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Abstract One of the most fundamental characteristics of a biomaterial tailored for bone repair and regeneration is its ability to promote bone regeneration and healing of large defects. This work reports producing a functionalized and hieratically porous bone scaffold that significantly supports cell adhesion and proliferation by providing bone mimicry structure and controlled release of protein. The Slit Guidance Ligand 3 (SLIT3) protein was previously tested to promote bone formation and control the resorption process in natural bone healing. In this study, our goal was to design a nanocomposite bone scaffold to be functionalized with SLIT3 protein and then evaluate the uptake and release profile from surface into culture media to support bone marrow-derived mesenchymal stem cells (MSC) 3D culture. Indirect 3D printing of a polylactic-co-glycolic acid (PLGA), hydroxyapatite nanoparticles, and polydopamine coated (PLGA-HANPs-PDA) was utilized to obtain a hierarchically porous and SLIT3 protein-releasing scaffold. The produced scaffold was evaluated and optimized using chemical, architectural, mechanical, and biological characterization techniques. Optimal physicochemical properties resulted in a unique microstructure with an average pore size of 178.06 ± 45 µm, 63% porosity, and stable and homogenous chemical composition. Mechanical testing demonstrated a compression strength up to 1.5 MPa at 75% strain, with a compression modulus of 0.58 ± 0.05 MPa. Preliminary biological experiments showed that the scaffold exhibited gradual SLIT3 protein release, biodegradability, and reliable biocompatibility for MSC cell culture. Finally, we showed for first time the bioactivity of SLIT3 protein within PLGA-HANPs-PDA scaffold to promote attachment and growth of mesenchymal stem cell (MSCs) seeded in bone mimicry scaffold matrix. The collected findings will serve as a bedrock for thorough and targeted in vitro studies to evaluate anticipated osteogenesis the MSCs.
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This content will become publicly available on June 23, 2026
Processing Collagen-Hydroxyapatite Composite for Bone Tissue Engineering: A 3D Printing Perspective
Tissue engineering is an interdisciplinary field combining biology, chemistry, and engineering to create implantable structures that support healing and regeneration. Autografts, tissues taken from a patient’s own body, are commonly used due to their high compatibility and minimal disease transmission risk. However, autografts are limited by the small amount of tissue that can be harvested. Allografts, or transplants from one person to another, provide a more natural alternative to synthetic or metal implants, yet their use is constrained by limited donor availability, high rejection rates, and significant operating costs. Although synthetic polymer, ceramic, and metallic implants have gained popularity due to their affordability and durability, they often lead to chronic pain, restricted movement, and eventual reimplantation because of issues like surface wear and reduced lubrication. Advances in artificial intelligence (AI), machine learning (ML), and 3D printing are opening new possibilities in tissue engineering. Researchers are now exploring natural polymers as an alternative to synthetic materials by focusing on the structural complexities and sustainability of native tissues. For example, type I collagen (Col), the most abundant protein in human connective tissues, shows promise as a replacement for titanium in bone tissue engineering due to its excellent mechanical properties, biocompatibility, and ability to support bone growth (osteogenesis). When combined with hydroxyapatite (HAp), Col-HAp composites can closely mimic the natural organic-inorganic structure of bone, providing both the chemical and physical properties needed to promote tissue healing and regeneration. However, the extraction and processing of collagen pose challenges, as they can degrade its natural properties and complicate the 3D printing of implants. This perspective examines the processing, characterization, and manufacturability of Col, its composites, and other robust biomaterials for bone tissue engineering, aiming to replicate the mechanical behavior of human limbs under both static and dynamic conditions. It also explores how AI and ML can enhance the precision and reproducibility of Col composite printing and enable generative scaffold design to foster vascularization, cell viability, and tissue growth. Finally, this work underscores the advancements in novel and customized 3D bioprinting systems designed to address patient-specific requirements, promote higher cell proliferation, and fabricate complex scaffold structures with improved structural properties.
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- Award ID(s):
- 2323731
- PAR ID:
- 10643099
- Publisher / Repository:
- American Society of Mechanical Engineers
- Date Published:
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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