Joseph Christakiran Moses

Cellular alignment through external stimulus offers dynamic control and functional adaptation that static topological or adhesive cues cannot provide. Static alignment strategies can impose defined cellular organization, but these cues are typically fixed after fabrication. By contrast, electric fields provide active bioelectrical cues that can modulate cell orientation, migration, and signaling, making them attractive for regulating cell alignment. However, current electrical‐stimulation platforms still provide limited capability to encode cell organization with microscale spatial precision. Here, we present a new light‐gated bioelectrical stimulation platform enabled by patterned photovoltaic microcell arrays. Those microcells transduce light into localized electric fields for microscale spatial modulation of cell (e.g., fibroblast) behavior pertient to cell orientation and migration. With pulsed light stimulation, the photovoltaic microcell arrays generate a photoelectrical response that can produce local electrical cues associated with pattern‐dependent alignment of fibroblasts perpendicular to the field lines. These results indicate that spatially patterned photovoltaic stimulation can be used not only to stimulate other cell types but also to influence fibroblast alignment and associated molecular responses upon illumination, without wired electrodes. Our study provides a wireless strategy for exploring fibroblast galvanotaxis and suggests a potential approach to guide fibroblast alignment and geometry‐dependent organization, and further tissue morphogenesis.

Poly(methyl methacrylate) (PMMA) bone cement is a biomaterial widely used for over 50 years to stabilize hip and knee implants or as a bone filler. PMMA was used initially in the form of PMMA plexiglass for submarines and airplanes, and, as the interest in the material increased, it was eventually used for medical applications. There are inherent issues with PMMA as a bone cement, including loosening of the prosthesis, a high rate of post-operative infections, differences in mechanical properties between bone and PMMA, and thermal necrosis of the surrounding tissue. Due to the inadequacies of PMMA-based bone cement, the scientific community has investigated combinatorial methods and multifunctional additives to improve the biomaterial's properties. This review evaluates the currently available multifunctional additives to PMMA-based bone cements. The described additives have multiple functions that can address issues with PMMA bone cement. Finally, insights into different additives at the clinical stage are described, highlighting the generation of additives currently being investigated for translating these technologies from bench to bedside.

The field of biofabrication is rapidly evolving, yet it faces persistent challenges, including long manufacturing latency, slow throughput, issues with reproducibility, and scalability limitations. High-throughput biofabrication (HTBF) has emerged as a powerful strategy which is presented here to address these gaps through a structured, three-tier framework. Tier 1 encompasses core HTBF methods, such as multi-modal bioprinting and robotic bioassembly, which enable the rapid fabrication of large, physiologically relevant tissue constructs. Tier 2 comprises assisting platforms, including microfluidics and microphysiological bioreactors, which provide perfusion, mechanical conditioning, multiplexable sensing, and process parallelization. Tier 3 represents HTBF outcomes, including organoids, organ-on-a-chip systems, and engineered tissue grafts that deliver clinically and pharmacologically relevant insights. These advancements enable the development of in-vitro models that streamline drug testing, making it more cost-effective and efficient, while enhancing the accuracy and reliability of preclinical drug evaluation. This review defines HTBF by outlining its core characteristics and framework, presenting insights into recent technological advancements and their applications in regenerative medicine and drug discovery. Additionally, it addresses the regulatory and clinical translation challenges that must be resolved to facilitate the adoption of HTBF in personalized healthcare.

The severe shortage of donor organs and limitations of current disease models highlight the urgent need for transformative strategies in tissue engineering (TE) and regenerative medicine (RM). Bioprinting has emerged as a powerful approach for creating functional tissues and organs, yet current workflows remain labor-intensive, variable, and challenging to scale. The convergence of artificial intelligence (AI), advanced bioprinting technologies, robotics, biosensing, and cutting-edge biological methods is catalyzing the development of self-driving bioprinting laboratories—a fully integrated, autonomous, closed-loop system capable of designing, fabricating, maturing, and assessing living tissue constructs, as well as supporting seamless transplantation, with minimal human intervention. By integrating autonomous cellular farming, on-demand bioink formulation, intelligent optical and digital reconstruction platforms, AI-driven bioprinting, intelligent bioreactors, and robotic transplantation within a sterile, interconnected ecosystem, such platforms can continuously learn, adapt, and optimize workflows, enabling standardized, scalable tissue manufacturing and facilitating a seamless transition from bench to bedside. This perspective outlines the foundational technologies, opportunities, and challenges for realizing self-driving bioprinting, envisioning a future where intelligent, automated platforms transform TE and RM into a scalable, predictive, and clinically integrated discipline at the forefront of precision medicine.

Electroconductive biomaterials (ECBs) recreate the bioelectrical microenvironment of nerve tissue, facilitating action potential propagation and enhancing regeneration via electrical stimulation (ES). We report a pseudocapacitive ECB with high conductivity, charge density, and low impedance, combining mixed electronic‐ionic transport with reversible redox activity to deliver stable ES without electrode degradation. The scaffold comprises aligned microfibrous polypyrrole (PPy) and Bombyx mori silk fibroin (BmSF), functionalized with Antheraea assamensis silk fibroin (AaSF) rich in RGD motifs. Anionic AaSF acts as a secondary dopant for PPy, improving electrical conductivity (∼9.18 mS cm ^{− 1} ) and charge‐transfer efficiency (∼24 Ω), while increasing charge injection at low potentials (∼0.5 µC cm ⁻² at 50 mV) beyond conventional bioelectrodes. Under pulsed ES at 50 mV cm ^{− 1} , primary dorsal root ganglion neurons extended neurites up to 830 µm in 7 days. Excessive current or voltage reduced outgrowth, underscoring the importance of ES optimization. Biocompatibility tests showed AaSF functionalization enhanced cell adhesion, reduced pro‐inflammatory responses, and promoted neuronal and glial differentiation of primary adipose‐derived mesenchymal stem cells via improved intercellular communication. This work links scaffold electrochemical properties to neuronal outcomes, providing a framework for selecting ES parameters in excitable tissues. The developed biohybrid scaffold offers a promising platform for next‐generation nerve guidance conduits in regenerative therapies.

Understanding the human distal lung requires ex-vivo models that capture both the structural hierarchy and mechanical environment of alveolar sacs, yet current ex-vivo systems fall short. Manually cultured organoids and two-dimensional cell cultures lack structural hierarchy, apical access, and physiologic actuation via ventilation, limiting their use in modeling infection and mechano-transduction. Here, we established three-dimensional (3D) alveolar epithelial sacculoids (AES) by bioprinting pluripotent stem cell-derived alveolar epithelial type II cells (ATIIs) into defined 3D geometries in high density. AES reproducibly self-organized into multi-unit, lumenized sacs with polarized epithelia, surfactant secretion, and functional heterogeneity including proliferative ATIIs, surfactant-producing ATIIs, and transitional pre-alveolar type I transitional cell state (PATS)-like cells. A custom air-driven platform enabled fluid-mediated 3D ventilation, producing volumetric oscillations across closed sacs. This actuation engaged canonical (Ser127) and non-canonical (Tyr357, integrin–FAK–dependent) Hippo signaling, driving ATII-to-ATI remodeling and junctional stabilization. Upon apical infection with influenza virus, AES recapitulated canonical antiviral responses and epithelial plasticity resembling injury-induced alveolar repair, including depletion of functional ATIIs and emergence of proliferative ATIIs and transitional states. AES represent a physiologically ventilated model of the human alveolar niche, enabling mechanistic studies of epithelial plasticity, viral pathogenesis, and biomechanical signaling under physiologically-relevant conditions. Overall, our model provides a foundation for future integration of stromal, vascular, and immune components toward full alveolar mimicry to facilitate ex-vivo translational respiratory research.

Organohydrogels are an emerging class of soft materials that mimick the mechanical durability and organic solvent affinity of organogels and the biocompatibility and water swelling ability characteristics of hydrogels for prospective biomedical applications. This work introduces a facile, catalyst-free one-step chemical approach to develop an organohydrogel with impeccable antibiofouling properties following the epoxy-amine ring-opening reaction under ambient conditions. The mechanical properties of the as-fabricated organohydrogel can be tailored depending on the concentration of the epoxy-based cross-linker, from 0.10 to 1.12 MPa (compressive modulus). The affinity of the as-developed organohydrogel to both organic solvents and water was exploited to incorporate the antimicrobial nitric oxide donor (NO) molecule, S-nitroso-N-acetylpenicillamine (SNAP) from ethanol, and subsequently, the water-sensitive NO-releasing behavior of the organohydrogels was analyzed. The SNAP-incorporated organohydrogels release physiologically active levels of NO with 3.13 ± 0.27 × 10^-10 and 0.36 ± 0.14 × 10^-10 mol cm^-2 min^-1 flux of NO release observed at 0 and 24 h, respectively. The as-reported organohydrogel demonstrated excellent antibacterial activity against Escherichia coli and Staphylococcus aureus with >99% and >87% reduction, respectively, without eliciting any cytotoxicity concerns. Moreover, the organohydrogel with remarkable water uptake capacity was extended as a coating on different medically relevant polymers to demonstrate transparent underwater superoleophobicity. Thus, the facile synthesis of the reported organohydrogel and its derived underwater antifouling coating can open avenues for utility in biomedical, energy, and environmental applications.

Nitric oxide (NO) is a potent gasotransmitter that exhibits a pleiotropic effect in regulating homeostasis and pathophysiology. Though it is a versatile biomaterial, silicone‐based devices are still challenged by implant‐associated infections and fibrous capsule formation complications. Here, a NO‐generating (NOgen) interface is developed from copper or strontium‐doped mesoporous bioactive glass‐based coating on silicone substrates to facilitate metal‐ion catalysis of endogenous S‐nitrosothiols. The copper or strontium‐based interfaces can generate physiologically relevant NO levels, which have bactericidal and antithrombotic effects to combat implant‐associated early onsite infection and thrombosis. The NO generated in tandem with the low therapeutic release of strontium ions from the NOgen interface regulates cellular fate pertaining to fibroblasts, macrophages, and endothelial cells. Strontium suppresses the collagen expression and migration of activated fibroblasts while favoring M ₂ phenotype bias in macrophages. Differential NO flux observed over time from NOgen interfaces helps switch macrophages from proinflammatory M ₁ phenotype to M ₂ anti‐inflammatory phenotype. Moreover, the synergistic effect of leachate and NO generated by the silicone substrate demonstrates a proangiogenic effect by aiding endothelial network maturation in vitro. Thus, the multifunctional features of the developed strontium‐doped bioactive glass‐based coating hold promise in regulating local immune‐micromilieu and attenuating implant‐associated fibrosis of silicone‐based implantable devices.

The epithelium is one of the important tissues in the body as it plays a crucial barrier role serving as a gateway into and out of the body. Most organs in the body contain an epithelial tissue component, where the tightly connected, organ-specific epithelial cells organize into cysts, invaginations, or tubules, thereby performing distinct to endocrine or exocrine secretory functions. Despite the significance of epithelium, engineering functional epithelium in vitro has remained a challenge due to it is special architecture, heterotypic composition of epithelial tissues, and most importantly, difficulty in attaining the apico-basal and planar polarity of epithelial cells. Bioprinting has brought a paradigm shift in fabricating such apico-basal polarized tissues. In this review, we provide an overview of epithelial tissues and provide insights on recapitulating their cellular arrangement and polarization to achieve epithelial function. We describe the different bioprinting techniques that have been successful in engineering polarized epithelium, which can serve as in vitro models for understanding homeostasis and studying diseased conditions. We also discuss the different attempts that have been investigated to study these 3D bioprinted engineered epithelium for preclinical use. Finally, we highlight the challenges and the opportunities that need to be addressed for translation of 3D bioprinted epithelial tissues towards paving way for personalized healthcare in the future.