The Journal of Applied Tissue Engineering

Dynamic Mechanical Stimulation of Fibroblasts in Aligned Scaffolds: Inhibiting the YAP/TAZ Pathway to Reduce Wound Contraction

kimia sadeghzadeh — 2026-10-05

Pathological scarring and wound contraction remain significant medical challenges, often resulting in functional impairment, loss of mobility, and aesthetic distress(1,2). Adult wound healing usually ends with fibrotic scars and disorganized collagen. In contrast, fetal healing happens without scarring. Why? Because fetal skin has a low-tension environment and special fibroblast lineages(3,4). Central to this biophysical regulation is the YAP/TAZ signaling pathway, a mechanosensitive molecular rheostat that senses matrix stiffness and tension to drive the myofibroblast phenotype(5,6,7). This review examines recent advancements in the synergistic use of aligned scaffold architectures and dynamic mechanical stimulation to guide cellular recruitment and maturation(8,9,10). Furthermore, we explore therapeutic strategies to inhibit the YAP/TAZ pathway—ranging from pharmacological agents like Verteporfin to "smart" drug-delivery nanogels—to interrupt the fibrotic feedback loop and steer the healing process toward functional skin regeneration(11,12,13).

Biomaterials and scaffolds that promote regenerative rather than fibrotic healing

ELNAZ ABEDINI — 2026-10-05

Wound healing after dermal wounding is a major clinical problem and for adult skin, healing reverts to fibrotic repair, which involves an excess of collagen deposition and an activation of myofibroblasts. Embryonic skin, on the other hand, quickly regenerates without scarring, with tightly regulated immune responses and balanced cytokine signaling. The biomaterial scaffolds have been developed to become active therapeutic platforms that can alter the course of the wound from fibrosis to regeneration by mimicking essential microenvironmental signals. Scaffold design principles (architecture, porosity, stiffness, and surface topography) are discussed and natural and synthetic biomaterials are reviewed for their ability to induce regeneration associated phenotypes. We highlight immune-modulatory strategies which switch macrophages to pro-resolving phenotypes and inhibit fibrotic cascade. In addition to state of the art fabrication technologies like 3D bioprinting and electrospinning, advanced biofunctionalization strategies like sustained delivery of anti-fibrotic growth factors, miRNA therapeutics and cell-seeded constructs are also critically evaluated. Preliminary data have shown that strategically designed scaffolds can markedly decrease scar index and restore skin appendages. Lastly, we discuss translational issues and trends for personalized, phase-dependent responsive scaffolds. This analysis emphasizes that biomaterial-directed regeneration is a pedagogic therapeutic model that can revolutionize scar management in the clinical practice.

Smart Scaffolds in Tissue Engineering: Stimuli-Responsive Platforms for Dynamic Tissue Regeneration

ELNAZ ABEDINI — 2026-10-05

Traditional scaffolds in tissue engineering are static structural supports and cannot cope with the changing physiological state of the wound or tissue formation. Smart scaffolds are able to adapt the physical or chemical form of a scaffold in response to the internal or external triggers. The design principles, material classes, and mechanisms of stimuli-responsive frameworks are discussed in this review. We analyze scaffolds responsive to pH, temperature, enzymes, reactive oxygen species, glucose, magnetic fields, electrical cues, mechanical force, and light. We also discuss multi-stimuli-responsive systems and 4D printing technologies. We also discuss translational barriers such as biocompatibility, long-term stability, scale-up, and regulatory complexity. The review ends with future aspirations for immuno-smart and sensor-integrated scaffolds. With the dynamic nature of biological processes, smart scaffolds allow the drug release, mechanical properties, and cell behavior to be controlled with precision.

Smart Electroactive Scaffolds: Integrating Electrical Signaling, Mechanical Responsiveness, and Biological Function for Next-Generation Regenerative Therapies

Zahra Barabadi — 2026-10-05

Abstract

The extracellular microenvironment is far more than a passive structural framework; it represents a dynamic and electromechanically active niche that influences cellular behavior, tissue organization, and regenerative processes. Although conventional polymeric scaffolds have been successful in reproducing key structural and biochemical features of native tissues, they have generally ignored the critical role of endogenous bioelectric signals that regulate fundamental biological events, including wound repair, neural development, and cardiac electrical synchronization. In recent years, a fundamental shift has emerged in tissue engineering, moving away from the concept of scaffolds as inert structural supports toward the development of electroactive and

This review examines the major classes of electroactive materials, including intrinsically conductive polymers, metal-enhanced electroactive polymers, carbon-based nanomaterials, piezoelectric ceramics and polymers, and emerging two-dimensional materials such as MXenes, with a focus on their physicochemical characteristics, fabrication strategies, and biological integration. A systematic literature search across PubMed/MEDLINE, Web of Science, Scopus, and IEEE Xplore was conducted to identify peer-reviewed studies on electroactive scaffolds published primarily between 2010 and 2026; eligible experimental and translational reports were screened, and data were extracted and synthesized narratively by material class, design strategy, and tissue application. We further discuss how electrical conductivity, piezoelectric responses, and stimuli-responsive properties can regulate cellular functions and enhance regeneration in neural, cardiac, musculoskeletal, and skin tissues. Particular attention is given to the relationship between material properties and electrical stimulation strategies, the development of self-powered and multifunctional scaffold systems, and the remaining challenges associated with clinical translation, including long-term material stability, manufacturing standardization, and regulatory considerations.

Vascularized Immunoprotective Biomaterials as a Platform for β-Cell and Islet Replacement Therapy in Diabetes: Mechanisms and Translational Potential

Hamideh Babaloo — 2026-10-05

Islet and β-cell replacement can restore physiological insulin secretion in type 1 diabetes, but donor scarcity, chronic immunosuppression, and the fragility of avascular grafts have kept the approach from becoming routine therapy. Biomaterial engineering has approached these problems from two directions historically treated as separate traditions: immunoisolation, which shields transplanted cells behind a permselective barrier, and vascularization, which restores the oxygen and nutrient supply lost when islets are stripped of their native microvasculature. This review argues that the two goals are mechanistically coupled, because the same barrier properties that exclude immune effectors also constrain the oxygen diffusion on which β-cell survival depends. We examine the biological barriers to graft survival, the determinants of islet revascularization, and the principal classes of immunoprotective biomaterials (macroencapsulation devices, microcapsules, nanothin conformal coatings, hydrogels, and decellularized matrices) with attention to the trade-offs each imposes between permeability, mechanical durability, and immune exclusion. We then synthesize emerging platforms that engineer vascularization and immunoprotection together: pro-angiogenic and oxygen-generating materials, prevascularized and device-less sites, and local immunomodulatory strategies designed to substitute for systemic immunosuppression. Evidence is graded from mechanistic and rodent studies through non-human primate and clinical data, and we discuss why encouraging preclinical results have translated unevenly into durable clinical benefit. We conclude that no single material property solves this problem in isolation; durable, immunosuppression-free β-cell replacement will likely require materials engineered simultaneously for vascular integration, immune modulation, and manufacturable reproducibility, alongside renewable stem-cell-derived cell sources.

Magnetically Responsive TPMS-Based Smart Scaffold for Bone Tissue Engineering: Numerical Investigation Using COMSOL Multiphysics

Abolfaazl Mirani — 2026-10-05

Magnetically responsive scaffolds have emerged as promising platforms in tissue engineering due to their ability to provide remote, non-invasive stimulation for regulating cellular behavior and enhancing tissue regeneration. In this study, a novel triply periodic minimal surface (TPMS)-based smart scaffold reinforced with superparamagnetic iron oxide nanoparticles (SPIONs) was designed and numerically investigated using COMSOL Multiphysics®. The scaffold architecture was optimized to combine high porosity, interconnected pore networks, and magnetic responsiveness for bone tissue engineering applications. A three-dimensional finite element model was developed to analyze magnetic flux density distribution, field intensity, and magnetic field propagation under an external static magnetic field. Simulations were performed using Cartesian, cylindrical, and spherical coordinate systems to comprehensively evaluate magnetic behavior within and around the scaffold structure. The results demonstrated homogeneous magnetic field penetration throughout the porous architecture, with localized magnetic flux enhancement observed at pore-wall intersections and regions of high curvature. The maximum magnetic flux density reached approximately 2.08 mT, which lies within the biologically effective range reported for osteogenic stimulation. The proposed scaffold generated controllable magnetic microenvironments capable of enhancing mechanotransduction pathways, promoting cell proliferation, and supporting bone regeneration. The findings suggest that TPMS-based magnetic scaffolds represent a promising strategy for next-generation smart biomaterials and magnetically controlled regenerative therapies.