2026· The Archives of Bone & Joint Surgery· Vol 14, pp. 380 - 386· 1 citation· 35 references
Medicine
TL;DR
This review highlights recent progress in 3D‑printed Alg-based scaffolds for BTE, emphasizing how advanced fabrication techniques and BGs incorporation contribute to improved biological performance and structural reinforcement.
Abstract
Bone is a mineralized connective tissue composed of osteoblasts, osteocytes, and osteoclasts, and its integrity is essential for structural and physiological function. Defects arising from trauma, tumors, or developmental abnormalities often require surgical reconstruction to restore normal performance. Autografts and allografts have long served as standard treatments for bone repair, however, their usefulness is restricted by limited availability, donor‑site complications, and the potential transmission of underlying diseases. These challenges have accelerated interest in bone tissue engineering (BTE) as an alternative strategy capable of enhancing regeneration while reducing postoperative risks. Advances in three‑dimensional (3D) printing have introduced powerful technique for fabrication of scaffolds with precisely controlled architectures and tunable mechanical and biological characteristics. This technology enables the creation of porous constructs that mimic the structural complexity of native bone, supporting cell infiltration, nutrient transport, and vascularization. Effective scaffolds for BTE must demonstrate biocompatibility, biodegradability, appropriate strength and stiffness, and the ability to promote osteogenesis and angiogenesis. Among natural polymers, alginate (Alg) has become a prominent candidate due to its inherent biocompatibility, degradability, abundance, low cost, and non‑immunogenic nature. Its versatility makes it suitable for developing customized 3D‑printed scaffolds. Additionally, bioactive glasses (BGs) are widely incorporated into composite scaffolds because their composition closely resembles the mineral phase of bone. BGs significantly enhance osteoconductivity, support mineral deposition, and can improve the mechanical resilience of polymer-based constructs. This review highlights recent progress in 3D‑printed Alg-based scaffolds for BTE, emphasizing how advanced fabrication techniques and BGs incorporation contribute to improved biological performance and structural reinforcement.
The worldwide incidence of bone disorders is increasing at an alarming rate, especially among the elderly and those with increased obesity and poor physical activity. Therefore, bone tissue engineering, the process of regenerating diseased or damaged bone, is gaining increasing attention from the scientific community. One of the critical components for tissue engineering is the scaffold, an artificial extracellular matrix that promotes bone formation and regeneration activities. Due to the increasing demands for bone repair, bone tissue scaffolds have been extensively studied in state-of-the-art literature. Nevertheless, many areas related to scaffold manufacturing still offer huge scope for scientific research and development. One such area is the bioprinting of scaffolds, which combines the advantages of three-dimensional printing and biomaterials to create an ideal tissue growth support environment for bone tissue regeneration. This review highlights recent advances in the bioprinting of scaffolds for bone tissue engineering. Taking different biomaterial-based scaffolds as a starting point, the latest research progress and breakthrough points for enhancing the mechanical properties and bioactivities of scaffolds are summarized. Recent scientific breakthroughs related to the tailoring and creative design of scaffolds have been highlighted. New strategies and schemes for subsequent bone scaffold angiogenesis and osteogenesis promotion for new bone tissue regeneration are also discussed. This comprehensive review identifies the shift of research direction, where the biological requirements such as immune response and vascularization is prioritized over fabrication methods. Research gaps on vascularization bottlenecks, methodological and evaluation gaps, fabrication challenges and regulatory hurdles have been identified as well. Future direction of research includes AI assisted design, 4D printing, smart implants, organoid integration and benchmarking standardization of bone tissue implants.
Md. Abu Shaid Sujon, Bin Wang, Hasibur R. Hamim et al.· Biomedical Materials· 0 citations
Bone scaffolds represent a common surgical approach for repairing bone defects, and the clinical demand for effective graft substitutes remains high due to the limited availability of autologous bone. Titanium (Ti) and its alloys are widely used as load‐bearing implants; however, their inherent biological inertness hinders early osteogenesis and delays osseointegration. With advances in bone tissue engineering, biofunctionalized 3D‐printed porous Ti scaffolds have emerged as a promising strategy to overcome these limitations. Among the various biomaterials investigated, silk fibroin (SF) has attracted considerable interest owing to its excellent biocompatibility, controllable biodegradability, tunable mechanical properties, and intrinsic capacity for drug loading. The integration of SF onto Ti scaffolds through coatings, hydrogels, or composite structures mitigates the biological inertness of Ti and confers additional functionalities, such as controlled drug release, osteogenic stimulation, and immunomodulation. This review summarizes the structural characteristics, drug‐delivery behavior, and degradation mechanisms of SF, and highlights current evidence on its osteogenic and anti‐inflammatory effects both in vitro and in vivo when combined with porous Ti scaffolds. Furthermore, we discuss emerging multifunctional strategies, including composite coatings incorporating hydroxyapatite, metal‐ion doping, and SF‐based hydrogel systems. Overall, this review provides comprehensive insights into SF‐enhanced Ti scaffolds for next‐generation bone repair.
Jia-Jun Liu, Yan Wang, Xin Li et al.· Macromolecular Bioscience· 0 citations
Critical-size long bone defects remain a major clinical challenge, with treatments such as autografts or distraction osteogenesis causing donor-site morbidity, infection, or failure to restore complex bone architecture. Tissue-engineered implants that recapitulate native fracture healing provide a promising solution. However, scalability for dense cellular constructs is lacking. To address this, we bioprinted high-cell-density implants using rheologically competent sacrificial alginate bioinks. The constructs were supported by partially crosslinked alginate during bioprinting and chondrogenic differentiation, after which selective EDTA-mediated alginate dissolution generated scaffold-free implants. Quality characterization confirmed chondro-osteogenic signatures and extracellular matrix gene upregulation. Upon in vivo implantation in immunocompromised mice, implants underwent endochondral ossification, forming cortical and trabecular bone with bone marrow compartments. Integration with a suspension bioreactor enabled production of human-sized proof-of-concept implants. This work establishes a scalable 4D biofabrication process that integrates 3D bioprinting with dissolvable sacrificial alginate bioinks and results in scaffold-free, bone-forming callus implants.
Andreas Dimopoulos, Konstantinos Ioannidis, Nikolaos S. Giakoumakis et al.· Trends in Biotechnology· 0 citations
Critical-sized bone defects (CSDs) fail to undergo spontaneous regeneration. Conventional treatment methods, including bone grafts, as well as therapies based on growth factors and cytokines often face serious limitations, including limited availability, immune rejection, high cost, and safety concerns. Although tissue engineering using scaffolds has emerged as a promising alternative, many scaffold-based approaches still rely on the incorporation of exogenous growth factors or cytokines to achieve adequate osteoinductive performance, adding complexity, cost, and potential safety concerns to the treatment. Moreover, invasive implantation techniques and use of toxic crosslinkers during scaffold fabrication present additional challenges. Herein, we report the development of a minimally invasive, injectable, and fully biocompatible hydrogel (CCD@HapSi). The hydrogel, formed via a simple Schiff-base reaction between carboxymethyl chitosan and oxidized dextran, incorporates nanohydroxyapatite and silica nanoparticles to impart osteoinductive, osteoconductive, and antibacterial functionality without the need for external crosslinkers or growth factors. CCD@HapSi exhibited ultrafast gelation, optimal mechanical strength, and controlled degradation, while supporting stem cell adhesion, proliferation, and upregulation of osteogenic genes. In vivo, the hydrogel promoted substantial bone regeneration in a critical sized calvarial defect, significantly outperforming control groups. These findings highlight CCD@HapSi as a safe, cost-effective, and clinically translatable platform for bone regeneration.
Malika Arora, Satish Kumar, Jijo Thomas et al.· International Journal of Bio...· 2 citations
Autologous and allogeneic bone grafts are primarily used for bone tissue defects; however, they have limitations such as limited supply, donor site morbidity, and immune rejection risks. Therefore, substitute synthetic bone grafts are required.
Using low-temperature 3D printing combined with freeze-drying technology, a hierarchically porous PLGA/HA@SeNPs composite scaffold was fabricated by compositing poly(lactic-co-glycolic acid) (PLGA) with hyaluronic acid-modified selenium nanoparticles (HA@SeNPs), enabling sustained immunomodulation and osteogenic activity through its engineered microtopography and bioactive components.
In vitro evaluations confirmed that the unique microstructure and sustained selenium release from HA@SeNPs synergistically promoted macrophage polarization toward the M2 phenotype, accompanied by enhanced osteogenic differentiation as shown by upregulation of Runx2 and OCN and accelerated matrix mineralization. Implantation into a rat femoral critical-sized defect model resulted in substantially improved bone repair and architectural restoration.
These findings indicate that the intrinsic physicochemical properties of the PLGA/HA@SeNPs scaffold orchestrate a favorable osteo-immune environment, positioning it as a promising platform for bone regeneration.
Shengwen Cheng, Yuqiao Wang, Yu Zhai et al.· Burns & Trauma· 0 citations
Alveolar ridge deficiency remains a significant clinical challenge in dental implantology, often necessitating bone augmentation procedures. While autogenous bone grafting is considered the gold standard, its limitations, including donor site complications and limited availability, have prompted the development of alternative bone graft materials. In this study, we fabricated a novel polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP)@zinc oxide (ZnO) composite scaffold via direct ink writing (DIW) three-dimensional (3D) printing. The scaffold integrates a biomimetic porous architecture with a controlled ion-release strategy to enhance osteogenic performance. The characterization of the material confirmed excellent chemical stability, hydrophilicity, and tunable degradation behavior. The incorporation of ZnO facilitated the sustained release of bioactive ions (Ca2+, PO4 3-, and Zn2+), significantly improving the scaffold's bioactivity. In vitro assessments revealed that the scaffold with 2% ZnO (PTZ-2) exhibited optimal cytocompatibility and osteogenic differentiation capacity, promoting alkaline phosphatase activity and mineralized nodule formation in MC3T3-E1 cells. In a rat cranial defect model, the PTZ-2 scaffold achieved approximately 95% new bone area after 12 weeks. Histological analysis further confirmed the presence of continuous, highly mineralized bone matrix with excellent osseointegration capability. These findings collectively indicate that the 3D-printed PCL/β-TCP@ZnO composite scaffold has great potential for clinical translation in bone defect regeneration.
