Biology subjects

Panebianco, C. J.

Publications and source records attributed to Panebianco, C. J..

7 recordsLinked to original sources

bioRxiv2026

Degeneration-Inspired Architectural States Defined by Voronoi Point Spacing and Surface-Mediated Rescue of Osteogenic Dysfunction in 3D-Printed Scaffolds

Osteoporotic bone degeneration involves progressive deterioration of trabecular microarchitecture, yet most scaffold-based bone tissue engineering studies evaluate osteogenesis in structurally favorable architectures that poorly represent compromised bone environments. Here, we establish a degeneration-inspired Voronoi scaffold platform in which point spacing serves as a single tunable architectural parameter to model transitions from dense mechanically integrated to severely deteriorated trabecular-like microenvironments. Increasing point spacing from 1.25 to 2.5 mm progressively reduced scaffold connectivity and stiffness while shifting deformation behavior from distributed load transfer to localized stress concentration, as confirmed by finite element analysis and mechanical testing. Benchmarking against clinically reported HR-pQCT datasets from postmenopausal women demonstrated that the intermediate 1.75 mm point spacing scaffold represents a clinically relevant compromised trabecular-like state, whereas the 2.5 mm scaffold represents a more severely deteriorated architectural condition. These architecture-dependent mechanical and structural transitions directly regulated hMSC behavior, where high point spacing scaffolds reduced cytoskeletal organization, stress fiber density, and osteogenic mineralization, establishing an architecture-associated osteogenic dysfunction regime. Polydopamine (PDA) coating progressively enhanced cytoskeletal organization and mineralization within architecturally compromised scaffolds without altering scaffold geometry. To quantitatively assess biointerface-mediated functional recovery, a Mineralization Rescue Percentage (MRP) framework was introduced, demonstrating up to 43% restoration of architecture-associated mineralization loss following PDA coating. Collectively, this work establishes a clinically contextualized degeneration-to-rescue biomaterials framework that shifts current scaffold design paradigms beyond structurally favorable architectures toward systematic investigation and functional rescue of architecture-associated osteogenic dysfunction within compromised bone-like microenvironments. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/725650v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@15b1204org.highwire.dtl.DTLVardef@1fbdce6org.highwire.dtl.DTLVardef@638215org.highwire.dtl.DTLVardef@f1370d_HPS_FORMAT_FIGEXP M_FIG C_FIG Statement of SignificanceMost scaffold-based bone tissue engineering studies evaluate osteogenesis in structurally favorable architectures that poorly represent compromised bone microenvironments associated with osteoporosis. Here, a clinically contextualized Voronoi scaffold platform is established in which point spacing serves as a single tunable architectural parameter to model transitions from mechanically integrated to structurally deteriorated trabecular-like states. By decoupling architectural and surface biointerface effects, the study demonstrates that architectural deterioration alone can drive cytoskeletal disruption and osteogenic failure. Importantly, polydopamine-mediated surface engineering partially restored cytoskeletal organization and mineralization within architecturally compromised scaffolds without altering bulk geometry. A Mineralization Rescue Percentage (MRP) framework was further introduced to quantitatively assess biointerface-mediated functional recovery within degeneration-inspired scaffold microenvironments.

bioengineering↗

bioRxiv2026

Plasma-Enabled Multiscale Coupling of Architecture and Biointerfaces Drives Osteogenesis in 3D-Printed Gyroid Scaffolds

Engineering functional bone scaffolds can be enhanced by integrating biologically instructive nanoscale surface features (e.g., nanotopography and nanoroughness), micro-scale geometric cues (e.g., curvature and porosity), and macro-scale mechanical properties (e.g., bulk stiffness); however, these length scales are often optimized independently. Here, we present a multiscale design framework combining additive manufacturing of triply periodic minimal surface (TPMS) gyroid scaffolds with plasma-assisted nanoscale surface engineering to regulate osteogenesis. Controlled variation in strut thickness generates distinct architectural regimes with coupled changes in curvature, porosity, and compressive modulus, recapitulating key aspects of trabecular bone mechanics. Micro-computed tomography confirms trabecular bone-like features, while finite element modeling and compression testing reveal that thinner architectures (0.6 mm) exhibit curvature-preserving geometry and distributed stress profiles favorable for cellular interaction. A low-temperature plasma electroless reduction (PER) strategy enables controlled silver nanoparticle deposition, while polydopamine-mediated adhesion ensures uniform and cytocompatible coatings. Notably, PDA-AgNP-functionalized 0.6 mm scaffolds significantly outperform unmodified and AgNP-only groups, exhibiting enhanced cytoskeletal organization, stress fiber formation, matrix mineralization, and osteogenic gene expression. These findings demonstrate that coupling nanoscale biointerface features with micro- and macro-scale architecture produces a synergistic enhancement in osteogenesis, providing a design framework for functional bone scaffolds. Table of Content GraphicsA plasma-enabled strategy integrates 3D-printed scaffold architecture with nanoscale surface engineering to enhance bone formation. By combining tunable structural design with uniform nanoparticle coating, the study shows that optimal biological responses occur only when mechanical and surface cues act together, highlighting a synergistic multiscale approach for designing advanced biomaterials for bone regeneration. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/718992v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1d29685org.highwire.dtl.DTLVardef@983752org.highwire.dtl.DTLVardef@15816f5org.highwire.dtl.DTLVardef@4b4f50_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Maternal exercise rescues fetal akinesia-impaired joint and bone development

Fetal movements exert mechanical forces that shape the developing skeleton. Conditions that impair fetal movements can cause skeletal defects, but interventions are limited. Here, we show that maternal wheel running exercise regulates fetal skeletal development in mice. In wild-type fetuses, maternal exercise stimulated joint and bone morphogenesis. We reasoned that these effects occurred through either indirect maternofetal communication or direct mechanical stimulation of the fetus. Maternal exercise did not alter placental measures of nutrient transport. However, in the Splotch-delayed (Spd) mouse model of fetal akinesia, which features intact maternofetal communication but lacks fetal movements, maternal exercise substantially rescued fetal akinesia-impaired joint and bone development and prevented disuse-induced resorption of the deltoid tuberosity. Further, direct mechanical stimulation of Spd limbs explanted from systemic factors similarly stimulated joint morphogenesis. Together, these findings identify maternal exercise as a regulator of fetal skeletal development, providing a platform for studying skeletal developmental mechanobiology and suggesting potential therapeutic applications for fetuses with impaired movement.

developmental biology↗

bioRxiv2024

Dynamics of postnatal bone development and epiphyseal synostosis in the caprine autopod

Bones develop to structurally balance strength and mobility. Bone developmental dynamics are influenced by whether an animal is ambulatory at birth (i.e., precocial). Precocial species, such as goats, develop advanced skeletal maturity in utero, making them useful models for studying the dynamics of bone formation under mechanical load. Here, we used microcomputed tomography and histology to characterize postnatal bone development in the autopod of the caprine lower forelimb. The caprine autopod features two toes, fused by metacarpal synostosis (i.e., bone fusion) prior to birth. Our analysis focused on the phalanges 1 (P1) and metacarpals of the goat autopod from birth through adulthood (3.5 years). P1 cortical bone densified rapidly after birth (half-life using one-phase exponential decay model ({tau}1/2 = 1.6 {+/-} 0.4 months), but the P1 cortical thickness increased continually through adulthood ({tau}1/2 = 7.2 {+/-} 2.7 mo). Upon normalization by body mass, the normalized polar moment of inertia of P1 cortical bone was constant over time, suggestive of structural load adaptation. P1 trabecular bone increased in trabecular number ({tau}1/2 = 6.7 {+/-} 2.8 mo) and thickness ({tau}1/2 = 6.6 {+/-} 2.0 mo) until skeletal maturity, while metacarpal trabeculae grew primarily through trabecular thickening ({tau}1/2 = 7.9 {+/-} 2.2 mo). Unlike prenatal fusion of the metacarpal diaphysis, synostosis of the epiphyses occurred postnatally, prior to growth plate closure, through a unique fibrocartilaginous endochondral ossification. These findings implicate ambulatory loading in postnatal bone development of precocial goats and identify a novel postnatal synostosis event in the caprine metacarpal epiphysis.

developmental biology↗

bioRxiv2024

YAP regulates periosteal expansion in fracture repair

Bone fracture repair initiates by periosteal expansion. The periosteum is typically quiescent, but upon fracture, periosteal cells proliferate and contribute to bone fracture repair. The expansion of the periosteum is regulated by gene transcription; however, the molecular mechanisms behind periosteal expansion are unclear. Here, we show that Yes-Associated Protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) mediate periosteal expansion and periosteal cell proliferation. Bone fracture increases the number of YAP-expressing periosteal cells, and deletion of YAP and TAZ from Osterix (Osx) expressing cells impairs early periosteal expansion. Mechanistically, YAP regulates both cell-intrinsic and cell-extrinsic factors that allow for periosteal expansion. Specifically, we identified Bone Morphogenetic Protein 4 (BMP4) as a cell extrinsic factor regulated by YAP, that rescues the impairment of periosteal expansion upon YAP/TAZ deletion. Together, these data establish YAP mediated transcriptional mechanisms that induce periosteal expansion in the early stages of fracture repair and provide new putative targets for therapeutic interventions.

cell biology↗

bioRxiv2024

Learning on a Limb: An outreach module to engage high school students in orthopaedics

Orthopaedic researchers need new strategies for engaging diverse students. Our field has demonstrated noticeable gaps in racial, ethnic, and gender diversity, which inhibit our ability to innovate and combat the severe socioeconomic burden of musculoskeletal disorders. Towards this goal, we designed, implemented, and evaluated Learning on a Limb, an orthopaedic research outreach module to teach diverse high school students about orthopaedic research. During the 4-hr module, students completed hands-on activities to learn how biomechanical testing, microcomputed tomography, cell culture, and histology are used in orthopaedic research. Over three years, we recruited 32 high school students from the Greater Philadelphia Area to participate in Learning on a Limb. Most participants identified as racial/ethnic or gender minorities in orthopaedic research. Using pre/post-tests, we found that students experienced significant learning gains of 51 percentage points from completing Learning on a Limb. In addition to teaching students about orthopaedic research, post-survey data demonstrated that participating in Learning on a Limb strongly influenced students interest in orthopaedic research. Several students acted on this interest by completing summer research experiences in the McKay Orthopaedic Research Laboratory at the University of Pennsylvania. Learning on a Limb instructors also benefited by having the opportunity to "pay it forward" to the next generation of students and build community within their department. Empowering institutions to host modules like Learning on a Limb would synergistically inspire diverse high school students and strengthen community within orthopaedic departments to ultimately enhance orthopaedic research innovations.

scientific communication and education↗

bioRxiv2024

Moesin activation controls bone resorption and tunneling nanotube-dependent osteoclast fusion

Cell-cell fusion is an evolutionarily conserved process that is essential for many functions, including fertilisation and the formation of placenta, muscle and osteoclasts, multinucleated cells that are unique in their ability to resorb bone. The mechanisms of osteoclast multinucleation involve dynamic interactions between the actin cytoskeleton and the plasma membrane that are still poorly characterized. Here, we found that moesin, a cytoskeletal linker protein member of the Ezrin/Radixin/Moesin (ERM) protein family, is activated during osteoclast maturation and plays an instrumental role in both osteoclast fusion and function. In mouse and human osteoclast precursors, moesin inhibition favors their ability to fuse into multinucleated osteoclasts. Accordingly, we demonstrated that moesin depletion decreases membrane-to-cortex attachment and enhances the formation of tunneling nanotubes (TNTs), F-actin-based intercellular bridges that we reveal here to trigger cell-cell fusion. Moesin also controls HIV-1- and inflammation-induced cell fusion. In addition, moesin regulates the formation of the sealing zone, the adhesive structure determining osteoclast bone resorption area, and thus controls bone degradation, via a {beta}3-integrin/RhoA/SLK pathway. Supporting our results, moesin-deficient mice present a reduced density of trabecular bones and increased osteoclast abundance and activity. These findings provide a better understanding of the regulation of cell-cell fusion and osteoclast biology, opening new opportunities to specifically target osteoclast activity in bone disease therapy.

cell biology↗