Wound healing is a complex natural process with overlapping sequences of inflammatory, proliferation, and remodeling stages. All stages involve immune cells and their secreted molecules, including macrophages, neutrophils, and cytokines. This process becomes dysregulated in chronic wounds, such as diabetic ulcers and malignant (fungating) wounds, where healing halts before it can be completed. Both generic immunomodulation and targeted immunoengineering approaches constitute a powerful toolbox to reset healing processes. This brief review first provides background on the involvement of immune system components contribute to wound healing and their dysregulation during impaired wound healing. It then discusses the current state of knowledge on immunomodulation and immunoengineering as applied to chronic wound care. The immunomodulation approach uses stem cells or extracellular vesicles to regulate inflammation and prevent cellular senescence so that tissue regeneration takes place. Immunoengineering approaches cover the use of DNA nanoparticles to aid tissue regeneration, and aptamer-antibody conjugates to control inflammation. Finally, theranostic devices which provide real-time sensing and delivery of necessary proteins and drugs to reset wound healing have been discussed.
I’jaaz Muhammad, Katherine Miller, Gang Ge, Thanh D. Nguyen, Kevin W.-H. Lo
Electrospinning has become one of the most common methods to fabricate piezoelectric polymer nanofibers for flexible electronics, sensors, energy harvesting devices, and bioelectronic scaffolds. Fiber alignment is one of many parameters that can impact nanofiber performance attributes since alignment affects mechanical anisotropy, crystal organization, and piezoelectric response. Nonetheless, few published works provide an in-depth discussion of collector rotation speed as it impacts nanofiber alignment, leaving detailed and reproducible methods for tuning alignment-dependent piezoelectric performance largely unreported. Here, we report a standardized electrospinning protocol to reproducibly fabricate piezoelectric nanofibers with controlled alignment through tuning the speed of a rotating collector. The steps in this protocol include preparing polymer solutions, setting up an electrospinning system, determining collector speed, collecting fibers, performing optional post-processing steps, and quantitatively evaluating fiber morphology and piezoelectric response. The protocol was validated through quantification of fiber alignment using scanning electron microscopy coupled with image-based orientation metrics, and piezoelectric performance through quantification of electrical output and piezoelectric coefficients. We demonstrated that increasing collector rotation speed from 1000 to 4000 rpm reduced orientation spread from 19.57° to 11.23°, and showed this increase in alignment was associated with an increase in the effective piezoelectric coefficient (d33) from 3.37 pC/N to 5.92 pC/N and an increase in open-circuit voltage output from 15 mV to 35 mV. These results highlight how the provided protocol enables users to reproducibly tune nanofiber orientation and associated piezoelectric performance. This protocol can aid in the design of scaffolds with tunable properties, wearable sensors, and mechanically-triggered energy harvesting devices.
Noelia Laura D’Elía, Pablo Postemsky, Javier Sartuqui, Damián Placente, Verónica Gonzalez-Pardo, Daniel Ercoli, Paula Verónica Messina
Oral diseases represent a significant public health challenge, particularly periodontal and peri-implant diseases that result in considerable bone loss and diminished quality of life. To address these issues, tissue engineering techniques such as guided bone regeneration (GBR) use barrier membranes to promote healing of bone defects. This study introduces a novel GBR membrane that employs Ganoderma sessile mycelium as a microstructural director of the biomaterial, yielding a mycelium-alginate-nanohydroxyapatite (My‐ALG‐HA) composite. The mycelium colonizes the ALG‐HA substrate, forming a porous trabecular bone-like network. Water contact angle assays indicated an anisotropic interaction behavior, and tensile testing confirmed the material ductility. Adding mycelium‐derived molecules increases the biomaterial’s hydrophobicity and improves its resistance to degradation under simulated physiological conditions. Additionally, an indirect crystal-violet assay using biomaterial dispersions showed osteoblast-like cell (MC3T3‐E1) cytocompatibility, highlighting its potential as an advanced solution for bone tissue regeneration in regenerative medicine. This approach combines the unique hierarchical structure and hydrophobic properties of Ganoderma mycelium alongside the cytocompatibility and hydrophilicity of the ALG‐HA system to improve structural integrity and biological functionality. These results establish a preliminary physicochemical basis for further optimization of wet‐state stability, suture retention and indirect cell-material interactions.
Akari J. Seiner, Victor Mishin, Shreya S. Soni, Elisabeth Posthill, Biplab Sarkar, Kara L. Spiller, Amy L. Throckmorton, Christopher B. Rodell
Hydrogels exhibit crosslink density-dependent properties that can be tuned to achieve spatiotemporal control, making them well-suited for a wide range of biomedical applications. In particular, light reactive hydrogels have requisite features for use in size-changing biomaterial devices such as pediatric blood shunts, that can uniquely meet evolving patient-specific needs after in vivo implantation. Here, we report on the design of a tunable photoresponsive and hemocompatible methacrylated dextran hydrogel suitable for use in such devices. The formation and subsequent deswelling of hydrogels proceeded through discrete sequential photopolymerization steps. The range of geometric tunability (up to 20% volume change) was a function of methacrylate density (e.g., polymer modification and concentration) and the extent of initial polymerization that was controlled via exposure time, intensity, and photoinitiator concentration. Furthermore, the hydrogels exhibited long-term (>3 months) stability and hemocompatibility, including with blood-borne cell types (e.g., erythrocytes and leukocytes). In vitro verification demonstrated the feasibility of this concept; our elucidation of the parameter space governing hydrogel properties will facilitate the use of the platform in various blood-interface constructs, specifically pediatric blood shunts.
Biomaterials are increasingly recognized as active immune-regulatory interfaces rather than passive structures tolerated by tissues. This Review develops the concept of programmable immune biointerfaces as material systems that organize immune-state behavior through coordinated mechanical, biochemical, structural, degradative, and stimulus-responsive cues. Mechanotransduction is presented as a central interface-to-cell signaling axis through which material properties are converted into immune-regulatory programs involving inflammatory activation, stromal remodeling, antigen presentation, fibrosis, suppression, and tissue integration. Stimuli-responsive materials extend this logic by enabling external or tissue-derived triggers to regulate when, where, and how immune-active signals are exposed, released, remodeled, or withdrawn. Regeneration and cancer illustrate divergent but related settings for engineered immune control: regenerative interfaces aim to support resolution, vascularization, matrix remodeling, and tissue integration, whereas cancer-associated interfaces model or redirect mechanically constrained, antigenically structured, and immunologically suppressive immune states. Finally, predictive programmable biocompatibility is framed as a design approach that links material variables, biological interface responses, immune-state outputs, AI-guided modeling, and closed-loop refinement. This framework shifts biocompatibility from tissue tolerance toward controllable immune-state trajectory design.
