Dopaminergic Axon Tracts Within a Hyaluronic Acid Hydrogel Encasement to Restore the Nigrostriatal Pathway.

Parkinson's disease is characterized by motor deficits emerging from insufficient dopamine in the striatum after degeneration of dopaminergic neurons and their long-projecting axons comprising the nigrostriatal pathway. To address this, a tissue-engineered nigrostriatal pathway (TE-NSP) featuring a tubular hydrogel with a collagen/laminin core that encases aggregated dopaminergic neurons and their axonal tracts is developed. This engineered microtissue can be implanted to replace neurons and axons with fidelity to the lost pathway and thus may provide dopamine according to feedback from host circuitry.

Generation of contractile forces by three-dimensional bundled axonal tracts in micro-tissue engineered neural networks.

Axonal extension and retraction are ongoing processes that occur throughout all developmental stages of an organism. The ability of axons to produce mechanical forces internally and respond to externally generated forces is crucial for nervous system development, maintenance, and plasticity. Such axonal mechanobiological phenomena have typically been evaluated at a single-cell level, but these mechanisms have not been studied when axons are present in a bundled three-dimensional (3D) form like in native tissue.

Silk Fibroin-Based Bioengineered Scaffold for Enabling Hemostasis and Skin Regeneration of Critical-Size Full-Thickness Heat-Induced Burn Wounds.

Millions of people around the globe are affected by full-thickness skin injuries. A delay in the healing of such injuries can lead to the formation of chronic wounds, posing several clinical and economic challenges. Current strategies for wound care aim for skin regeneration and not merely skin repair or faster wound closure.

Harnessing Multifaceted Next-Generation Technologies for Improved Skin Wound Healing.

Dysregulation of sequential and synchronized events of skin regeneration often results in the impairment of chronic wounds. Conventional wound dressings fail to trigger the normal healing mechanism owing to the pathophysiological conditions. Tissue engineering approaches that deal with the fabrication of dressings using various biomaterials, growth factors, and stem cells have shown accelerated healing outcomes.

Restoring lost nigrostriatal fibers in Parkinson's disease based on clinically-inspired design criteria.

Parkinson's disease is a neurodegenerative disease affecting around 10 million people worldwide. The death of dopaminergic neurons in the substantia nigra and the axonal fibers that constitute the nigrostriatal pathway leads to a loss of dopamine in the striatum that causes the motor symptoms of this disease. Traditional treatments have focused on reducing symptoms, while therapies with human fetal or stem cell-derived neurons have centered on implanting these cells in the striatum to restore its innervation.

Insight into Silk-Based Biomaterials: From Physicochemical Attributes to Recent Biomedical Applications.

Silk, a natural biopolymer, has been used clinically as suture material over thousands of years and has received much impetus for a plethora of biomedical applications in the last two decades. Silk protein isolated from both mulberry and nonmulberry silkworm varieties gained recognition as a potential biomaterial owing to its affordability and remarkable physicochemical properties. Molecular studies on the amino acid composition and conformation of silk proteins interpreted in the present review provide a critical understanding of the difference in crystallinity, hydrophobicity, and tensile strength among silkworm silk proteins.

Silk biomaterials in wound healing and skin regeneration therapeutics: From bench to bedside.

Silk biomaterials are known for biomedical and tissue engineering applications including drug delivery and implantable devices owing to their biocompatible and a wide range of ideal physico-chemical properties. Herein, we present a critical overview of the progress of silk-based matrices in skin regeneration therapeutics with an emphasis on recent innovations and scientific findings. Beginning with a brief description of numerous varieties of silks, the review summarizes our current understanding of the biological properties of silk that help in the wound healing process.

Silkworm Silk Scaffolds Functionalized with Recombinant Spider Silk Containing a Fibronectin Motif Promotes Healing of Full-Thickness Burn Wounds.

Full-thickness cutaneous wounds, such as deep burns, are complex wounds that often require surgical interventions. Herein, we show the efficacy of acellular grafts that can be made available off-the-shelf at an affordable cost using silk biomaterials. Silkworm silk fibroin (SF), being a cost-effective and natural biopolymer, provides essential features required for the fabrication of three-dimensional constructs for wound-healing applications.

Silkworm Silk Matrices Coated with Functionalized Spider Silk Accelerate Healing of Diabetic Wounds.

Complex cutaneous wounds like diabetic foot ulcers represent a critical clinical challenge and demand a large-scale and low-cost strategy for effective treatment. Herein, we use a rabbit animal model to investigate efficacy of bioactive wound dressings made up of silk biomaterials. Nanofibrous mats of silkworm silk fibroin (AaSF) are coated with various recombinant spider silk fusion proteins through silk-silk interactions to fabricate multifunctional wound dressings.

Emerging and innovative approaches for wound healing and skin regeneration: Current status and advances.

Current advances in skin tissue engineering and wound healing augur well for the development of split or full thickness skin substitutes to recapitulating the native functional skin. These engineered skin substitutes have fared successfully in recent years with exploration of various emerging technologies. As a result, recent clinical practice has been highly evolved incorporating various engineered skin substitutes as an adjunct to accelerate healing and improvement of quality of life in long-term.

Comprehensive Review on Silk at Nanoscale for Regenerative Medicine and Allied Applications.

Materials at the nanoscale offer numerous avenues to be explored and exploited in diverse realms. Among others, proteinaceous biomaterials such as silk hold immense prospects in the domain of nanoengineering. Silk offers a unique combination of desirable facets like biocompatibility; extraordinary mechanical properties, such as elongation, elasticity, toughness, and modulus; and tunable biodegradability which are far better than most naturally occurring and engineered materials.

Magnetic Actuator Device Assisted Modulation of Cellular Behavior and Tuning of Drug Release on Silk Platform.

Externally applied physical forces and mechanical stimulations have been found to be instructive to cells which lead to their signaling or differentiation. Further, bioreactors and functional biomaterials have been designed based on this principle to modulate cellular behavior under in vitro conditions. Herein, we have designed a magnetic actuator device (MAD) to understand the fundamental responses of two different phenomena: the effect of actuation on cardiac muscle cells and drug delivery under the influence of pulsed magnetic field.

In Situ Forming Injectable Silk Fibroin Hydrogel Promotes Skin Regeneration in Full Thickness Burn Wounds.

Full-thickness skin wounds, associated with deep burns or chronic wounds pose a major clinical problem. Herein, the development of in situ forming hydrogel using a natural silk fibroin (SF) biomaterial for treating burn wounds is reported. Blends of SF solutions isolated from Bombyx mori and Antheraea assama show inherent self-assembly between silk proteins and lead to irreversible gelation at body temperature.

Recombinant Spider Silk Functionalized Silkworm Silk Matrices as Potential Bioactive Wound Dressings and Skin Grafts.

Silk is considered to be a potential biomaterial for a wide number of biomedical applications. Silk fibroin (SF) can be retrieved in sufficient quantities from the cocoons produced by silkworms. While it is easy to formulate into scaffolds with favorable mechanical properties, the natural SF does not contain bioactive functions.

Potential of silk sericin based nanofibrous mats for wound dressing applications.

Wound dressing developed using bioactive materials has been a current area of research for treating chronic non-healing wounds owing to its high demand. Here, we report the fabrication and evaluation of nanofibrous matrix based wound dressings using biopolymer poly(vinyl alcohol) (PVA) incorporated with silk sericin (SS). SS extracted from the cocoons of mulberry variety Bombyx mori and non-mulberry variety Antheraea assama has been used to develop two types of blended mats.

Functionalized PVA-silk blended nanofibrous mats promote diabetic wound healing via regulation of extracellular matrix and tissue remodelling.

Chronic cutaneous ulcers, a complex pathophysiological diabetic condition, represent a critical clinical challenge in the current diabetes mellitus pandemic. Consequently, there is a compelling need for bioactive dressings that can trigger healing processes for complete wound repair. Silk fibroin (SF), a natural protein polymer from mulberry and non-mulberry silkworms, has properties that support accelerated wound healing rate.

Silk-Silk Interactions between Silkworm Fibroin and Recombinant Spider Silk Fusion Proteins Enable the Construction of Bioactive Materials.

Natural silk is easily accessible from silkworms and can be processed into different formats suitable as biomaterials and cell culture matrixes. Recombinant DNA technology enables chemical-free functionalization of partial silk proteins through fusion with peptide motifs and protein domains, but this constitutes a less cost-effective production process. Herein, we show that natural silk fibroin (SF) can be used as a bulk material that can be top-coated with a thin layer of the recombinant spider silk protein 4RepCT in fusion with various bioactive motifs and domains.

Tissue Engineered Skin and Wound Healing: Current Strategies and Future Directions.

The global volume of skin damage or injuries has major healthcare implications and, accounts for about half of the world's annual expenditure in the healthcare sector. In the last two decades, tissue-engineered skin constructs have shown great promise in the treatment of various skin-related disorders such as deep burns and wounds. The treatment methods for skin replacement and repair have evolved from utilization of autologous epidermal sheets to more complex bilayered cutaneous tissue engineered skin substitutes.

Role of non-mulberry silk fibroin in deposition and regulation of extracellular matrix towards accelerated wound healing.

Unlabelled: Bombyx mori silk fibroin (BMSF) as biopolymer has been extensively explored in wound healing applications. However, limited study is available on the potential of silk fibroin (SF) from non-mulberry (Antheraea assama and Philosamia ricini) silk variety. Herein, we have developed non-mulberry SF (NMSF) based electrospun mats functionalized with epidermal growth factor (EGF) and ciprofloxacin HCl as potential wound dressing.