Contact

  • Academic
    rimuniz@stanford.edu
    University - Student Department: School of Medicine Position: Graduate, Medicine

All Publications

  • A bioactive intramedullary implant enables accelerated bone regeneration and early load-bearing in distraction osteogenesis. Acta biomaterialia Uno, T., Lee, T. C., Shah, K., Chen, A. A., Lui, E., Alizadeh, H. V., Li, J., Muniz, R., Zhao, P., Pérez, A. S., Maekawa, H., Kim, S., Cherief, M., Regan, D. P., Takakubo, Y., Takagi, M., James, A., Young, J. L., Gardner, M. J., Mohler, D. G., Maloney, W. J., Yang, Y. P. 2026

    Abstract

    Distraction osteogenesis (DO) remains limited by prolonged consolidation and delayed bone union. This study evaluated whether a biodegradable, bone morphogenetic protein-2 (BMP-2)-releasing intramedullary implant (IMI) could enhance bone regenerate formation in a rat monofocal femoral lengthening model. We developed a Hybrid Tissue Engineering Construct (HyTEC) comprising a 3D-printed polycaprolactone-β-tricalcium phosphate IMI coated with a BMP-2-loaded hydrogel. Rats underwent standardized lengthening in three groups: control (DO only), IMI (implant without BMP-2), and IMI-BMP2 (BMP-2-releasing implant), with evaluation at postoperative days 31 and 52. The IMI-BMP2 group demonstrated significantly superior osteogenesis, achieving a bone volume fraction of 80 ± 22% at day 31, compared to 35 ± 19% (IMI) and 54 ± 25% (control), indicating accelerated regenerate formation. Radiographic and histological analyses confirmed early, uniform callus formation, while immunohistochemistry revealed elevated osteocalcin expression. Mechanical testing demonstrated restoration of approximately 50% of normal bone strength by day 52. Transcriptomic profiling revealed an exploratory BMP-2-associated regenerative gene signature, suggesting coordinated early-phase regulation of remodeling and metabolic reprogramming. This bioactive implant accelerated bone union, facilitated improved early ambulation consistent with partial mechanical competence restoration, and significantly shortened consolidation time, representing a promising clinically translatable strategy to overcome conventional DO limitations and improve patient outcomes. STATEMENT OF SIGNIFICANCE: Distraction osteogenesis is an effective strategy for managing large bone defects, but its clinical use is limited by prolonged consolidation and delayed functional recovery. This study presents a biodegradable intramedullary implant that provides sustained bone morphogenetic protein-2 (BMP-2) delivery and markedly accelerates regenerate formation, improves early mechanical strength, and enables earlier weight-bearing in a rat femoral lengthening model. In addition to demonstrating therapeutic efficacy, the work identifies a BMP-2-associated regenerative transcriptional signature linked to remodeling, osteoclast activity, and metabolic reprogramming. These findings establish a clinically translatable biomaterial-based approach to shorten treatment time and improve outcomes in distraction osteogenesis.

    View details for DOI 10.1016/j.actbio.2026.07.047

    View details for PubMedID 42526824

  • 3D Hybrid Bioprinting for Complex Multi-Tissue Engineering. bioRxiv : the preprint server for biology Alizadeh, H. V., Flores Pérez, A. S., Uno, T., Muniz, R. S., Kwon, S. H., Balachandar, A., Riley, N., Le, C. A., Li, J., Zhao, P., Lui, E., Kim, C., Moeinzadeh, S., Pan, C. C., Bhutani, N., Chu, C., Kim, S., Yang, Y. P. 2025

    Abstract

    3D bioprinting has revolutionized tissue engineering, enabling intricate, physiologically relevant constructs unattainable with conventional techniques, yet it remains limited in integrating soft and rigid multifunctional components for complex multi-tissue applications. In this study, we introduce a 3D hybrid bioprinting approach implementing the Hybprinter platform, which integrates multiple 3D printing modules under optimized conditions for a continuous bioprinting process with multiple soft and hard biomaterials. This approach demonstrates robust biocompatibility and broad tissue engineering potential for modeling and therapeutic applications. The capacity to fabricate multi-hydrogel hybrid constructs is illustrated by representative examples highlighting vascularization, multifunctionality, mechanical robustness, and implant suturability. Notably, compared with commonly fabricated hydrogel-only constructs, the resulting hybrid constructs achieve over a 1000-fold increase in mechanical strength, and demonstrated enhanced osteogenic differentiation, underscoring their suitability for load-bearing musculoskeletal and orthopedic tissue engineering. Additionally, cell-laden hydrogel constructs demonstrated robust chondrogenic differentiation, highlighting the capacity for lineage-specific tissue development in vitro. Beyond these outcomes, the presented hybrid bioprinting approach integrates essential tissue engineering attributes that unites mechanical robustness and suturable capacity with multi-material integration, gradient property design, incorporation of bioactive agents, and support for multi-cell loading. This versatile platform advances complex tissue engineering and holds promise for patient specific, organ-on-demand applications.

    View details for DOI 10.1101/2025.11.06.682452

    View details for PubMedID 41278903

    View details for PubMedCentralID PMC12637617