Critical Bone Defects Research Articles

3D-Printed Bifunctional Scaffold for Treatment of Critical Bone Defects Based on Osteoimmune Microenvironment Regulation and Osteogenetic Effects.

The critical-sized bone defect resulting from trauma, tumor resection, and congenital deformity fails to undergo spontaneous healing due to its substantial size, while the ensuing inflammatory process and hypoxic environment further impede the regenerative process. Therefore, it has consistently presented a significant clinical challenge. In the present study, we incorporate a glycyrrhizic acid (GA)-functionalized hydrogel onto the surface of a Hydroxyapatite (Hap)-modified Polycaprolactone (PCL) scaffold to fabricate a composite scaffold. The composed scaffold showed favorable anti-inflammatory and antioxidative capabilities by modulating macrophage polarization and scavenging reactive oxygen species (ROS); the modification of Hap enhanced its osteogenic ability. An in vivo rat skull defect model confirmed that the composed scaffold efficiently promotes bone regeneration. In general, the composed scaffold with the ability of osteoimmune microenvironment regulation can effectively repair critical-sized bone defects. This strategy provides a promising method for the reconstruction of large segmental bone defects.

One-Step Gas Foaming Strategy for Constructing Strontium Nanoparticle Decorated 3D Scaffolds: a New Platform for Repairing Critical Bone Defects.

The management of critical-sized bone defects poses significant clinical challenges, particularly in the battlefield and trauma-related injuries. However, bone tissue engineering scaffolds that satisfy high porosity and good angiogenic and osteogenic functions are scarce. In this study, 3D nanofiber scaffolds decorated with strontium nanoparticles (3DS-Sr) were fabricated by combining electrospinning and gas foaming. Sodium borohydride (NaBH4) served a dual role as both a reducing and gas-foaming agent, enabling a one-step process for expansion and modification. In vitro experimental results demonstrated that 3DS-Sr possessed an integrated multilayered porous structure. It promoted angiogenesis by upregulating the expression of hypoxia-inducible factor-1α (HIF-1α) protein and phosphorylation of ERK through the sustained release of Sr2+ and created a favorable microenvironment for osteogenesis by activating the Wnt/β-catenin pathway. In vivo experiments indicated that 3DS-Sr promoted cranial bone regeneration by synergistically promoting the effects of vascularization and osteogenesis. In summary, this study proposed a bioactive bone scaffold in a "one stone, two birds" manner, providing a promising strategy for bone defect repair.

A Stone‐Cottage‐Inspired Printing Strategy to Build Microsphere Patterned Scaffolds for Accelerated Bone Regeneration

AbstractThe physical microtopography, in an effective and stable manner, can powerfully confer biomaterials with enhanced osteoconduction for the repair of critical‐sized bone defects. However, the realization of the osteoconductive microtopography within a 3D porous scaffold is still unmet. Herein, this work presents a stone‐cottage‐inspired printing strategy to build microsphere patterned scaffolds with a tunable microtopography for accelerated bone regeneration. The customized composite inks of poly (lactic‐co‐glycolic acid) microspheres as “Stone” and alginate hydrogels as “Mortar” endow the fibers of as‐printed scaffolds with a stable and tunable groove‐ridge microstructure. Owing to this microtopography, microsphere patterned scaffolds significantly promote cell recruitment, immune response, angiogenesis, and osteogenesis. Meanwhile, compared to 55 and 85 µm, 25 µm width of groove‐ridge microstructure displays the most osteoconduction for repair of critical bone defects. Mechanistically, while cells prefer to adhere to microstructure with a bigger width and higher modulus in the early phase, this microstructure should also act as a barrier for cell growth and its smaller width is more beneficial for cell communication and differentiation in the later phase. Overall, it provides a robust strategy to fabricate the osteoconductive microtopography within a 3D scaffold, broadening the manipulation of physical morphology in tissue engineering.

Bone Regeneration with Dental Pulp Stem Cells in an Experimental Model

Background/Objectives: The therapeutic approach to bone mass loss and bone’s limited self-regeneration is a major focus of research, emphasizing new biomaterials and cell therapy. Tissue bioengineering emerges as a potential alternative to conventional treatments. In this study, an experimental model of a critical bone lesion in rats was used to investigate bone regeneration by treating the defect with biomaterials Evolution® and Gen-Os® (OsteoBiol®, Turín, Italy), with or without mesenchymal stromal cells from dental pulp (DP-MSCs). Methods: Forty-six adult male Wistar rats were subjected to a 5-mm critical bone defect in the right mandible, which does not regenerate without intervention. The rats were randomly assigned to a Simulated Group, Control Group, or two Study Groups (using Evolution®, Gen-Os®, and DP-MSCs). The specimens were euthanized at three or six months, and radiological, histological, and ELISA tests were conducted to assess bone regeneration. Results: The radiological results showed that the DP-MSC group achieved uniform radiopacity and continuity in the bone edge, with near-complete structural defect restitution. Histologically, full bone regeneration was observed, with well-organized, vascularized lamellar bone and no lesion edges. These findings were supported by increases in endoglin, transforming growth factor-beta 1 (TGF-β1), protocollagen, parathormone, and calcitonin, indicating a conducive environment for bone regeneration. Conclusions: The use of DP-MSCs combined with biomaterials with appropriate three-dimensional matrices is a promising therapeutic option for further exploration.

3D-printed magnesium-doped micro-nano bioactive glass composite scaffolds repair critical bone defects by promoting osteogenesis, angiogenesis, and immunomodulation

Magnesium ions play an important immune-regulatory role during bone repair. For this study, we prepared micro-nano bioactive glass (MNBG) containing magnesium, which can release magnesium, silicon, and calcium ions and has a positive impact on osteogenic differentiation and vascular regeneration. In this study, MgMNBG was compounded and combined with poly(lactic-co-glycolic acid (PLGA) and polycaprolactone (PCL) for 3D printing. Afterwards, the physicochemical properties and bone repair performance of the scaffolds were evaluated throughin vitroandin vivoexperiments. We also investigated the effects of MgMNBG on osteogenic differentiation, immune regulation, and vascular regeneration. The results showed that MgMNBG can inhibit inflammation and promote osteogenesis and angiogenesis by regulating macrophages. PLGA/PCL/MgMNBG scaffolds have good osteogenic and angiogenic effects, and the composite scaffolds have excellent bone repair performance and potential application value.

Synthetic Bone Blocks Produced by Additive Manufacturing in the Repair of Critical Bone Defects.

This study evaluated the efficacy of synthetic bone blocks, composed of hydroxyapatite (HA) or β-tricalcium phosphate (B-TCP), which were produced by additive manufacturing and used for the repair of critical size bone defects (CSDs) in rat calvaria. Sixty rats were divided into five groups (n = 12): blood clot (CONTROL), 3D-printed HA (HA), 3D-printed β-TCP (B-TCP), 3D-printed HA + autologous micrograft (HA+RIG), and 3D-printed β-TCP + autologous micrograft (B-TCP+RIG). CSDs were surgically created in the parietal bone and treated with the respective biomaterials. The animals were euthanized at 30 and 60 days postsurgery for microcomputed tomography (micro-CT) histomorphometric, and immunohistochemical analysis to assess new bone formation. Micro-CT analysis showed that both biomaterials were incorporated into the animals' calvaria. The HA+RIG group, especially at 60 days, exhibited a significant increase in bone formation compared with the control. The use of 3D-printed bioceramics resulted in thinner trabeculae but a higher number of trabeculae compared with the control. Histomorphometric analysis showed bone islands in close contact with the B-TCP and HA blocks at 30 days. The HA blocks (HA and HA+RIG groups) showed statistically higher new bone formation values with further improvement when autologous micrografts were included. Immunohistochemical analysis showed the expression of bone repair proteins. At 30 days, the HA+RIG group had moderate Osteopontin (OPN) staining, indicating that the repair process had started, whereas other groups showed no staining. At 60 days, the HA+RIG group showed slight staining, similar to that of the control. Osteocalcin (OCN) staining, indicating osteoblastic activity, showed moderate expression in the HA and HA+RIG groups at 30 days, with slight expression in the B-TCP and B-TCP+RIG groups. The combination of HA blocks with autologous micrografts significantly enhanced bone repair, suggesting that the presence of progenitor cells and growth factors in the micrografts contributed to the improved outcomes. It was concluded that 3D-printed bone substitute blocks, associated with autologous micrografts, are highly effective in promoting bone repair in CSDs in rat calvaria.

Biomimetic mineralization of collagen from fish scale to construct a functionally gradient lamellar bone-like structure for guided bone regeneration

Wide used guided bone regeneration (GBR) membrane materials, such as collagen, Teflon, and other synthesized polymers, present a great challenge in term of integrating the mechanical property and degradation rate when addressing critical bone defects. Therefore, inspired by the distinctive architecture of fish scales, this study utilized epigallocatechin gallate to modify decellularized fish scales following biomimetic mineralization to fabricate a GBR membrane that mimics the structure of lamellar bone. The structure, physical and chemical properties, and biological functions of the novel GBR membrane were evaluated. Results indicate that the decellularized fish scale with 5 remineralization cycles (5R-E-DCFS) exhibited a composite and structure similar to natural bone and had a special functionally gradient mineral contents character, demonstrating excellent mechanical properties, hydrophilicity, and degradation properties. In vitro, the 5R-E-DCFS membrane exhibited excellent cytocompatibility promoting Sprague-Dawley (SD) rat bone marrow mesenchymal stem cell proliferation and differentiation up-regulating the expression of osteogenic-related genes and proteins. Furthermore, in vivo, the 5R-E-DCFS membrane promoted the critical skull bone defects of SD rats repairment and regeneration. Therefore, this innovative biomimetic membrane holds substantial clinical potential as an ideal GBR membrane with mechanical properties for space-making and suitable degradation rate for bone regeneration to manage bone defects.

Main Surgical Methods of Critical Tibial Bone Defects Replacement (Literature Review). Part II

Summary. This part of literature review is devoted to the main methods of critical bone defects replacement of the tibia, which cannot be repaired by using bone autoplasty. A search in the PubMed database for the period 2010 - 2023 was carried out, with preference given to the material from the last 5 years; the advantages and disadvantages of the most popular methods of treatment are shown. This article provides a descriptive, non-systematic review of the current literature on methods of tibial bone defect replacement and possible directions for future research. A thorough search in the PubMed database was performed using relevant search terms, with peer-reviewed articles in English identified and evaluated. No strict inclusion or exclusion criteria were used to select articles for a full-text review. Instead, a subjective assessment of the relevance of individual articles to the overall narrative and surgical techniques review was made, which ultimately resulted in 40 articles being referenced.

Hoxc10-mediated 'positional memory' regulates cartilage formation subsequent to femoral heterotopic grafting.

The Hox gene plays a crucial role in the bone development, determining their structure and morphology. Limb bone grafts expressing Hox positive genes are commonly used for free transplantation to repair Hox negative mandibular critical bone defects. However, the specific role of original Hox genes in newly formed bone during the cross-layer bone grafting healing process remains unexplored. Our findings demonstrate that femurs ectopically grafted into the mandibular environment retained a significant ability to differentiate into cartilage and form cartilaginous callus, which may be a key factor contributing to differences in bone graft healing. Hoxc10, an embryonic layer-specific genes, regulates cartilage formation during bone healing. Mechanistically, we observed Hoxc10 retention in co-cultured femoral BMSCs. Knocking out Hoxc10 narrows the bone gap and reduces cartilage formation. In summary, we reveal Hoxc10's 'positional memory' after adult cross-layer bone graft, influencing the outcomes of autologous bone graft.

Injectable, oxygen-releasing, thermosensitive hydrogel promotes vascularized bone formation with prolonged oxygen delivery and improved osteoinductivity

The failure or delay in healing of critical bone defects is primarily due to early local anoxic conditions and reduced osteogenic activity. In this research, we integrated calcium peroxide (CPO) embedded polycaprolactone (PCL) microspheres and osteoinductive nanoparticles (Hydroxyapatite/Laponite) into a thermosensitive hydrogel (Pluronic F127), thereby formulating an injectable oxygen-releasing osteogenic thermosensitive hydrogel. Notably, the oxygen-releasing microspheres (ORMs) within the composite hydrogel provide stable oxygen release for up to 21 days, ensuring the survival, migration, and bioactivity of both mesenchymal stem cells and endothelial cells under anoxic conditions. Additionally, the composite hydrogel significantly augments the osteogenic potential of bone marrow mesenchymal stem cells by providing a biomimetic microenvironment with the incorporation of nano-hydroxyapatite/laponite. Ultimately, the injectable composite hydrogel successfully stimulated bone regeneration within a cranial defect in a rat model after 8 weeks, with enhanced vascularization and bone quality. The engineered hydrogel provides a minimally invasive approach to stimulate bone regeneration with a sustained oxygen supply and osteogenic microenvironment provision, underlining its potential for treating critical bone defects.

Regeneration of Critical Calvarial Bone Defects Using Bovine Xenograft, Magnesium-Enriched Bovine Xenograft and Autologous Dentin in Rats: Micro-CT, Gene Expression and Immunohistochemical Analysis.

The aim of this study was to evaluate the efficacy of autologous dentin (AD), bovine xenograft (BX) and magnesium-enriched bovine xenograft (BX + Mg) in the healing of critical cranial bone defects (CCBDs) in rats. Eighty male Wistar rats were divided into four groups: BX, BX + Mg, AD and the control group (no intervention). Eight mm CCBDs were created and treated with the respective biomaterials. Healing was assessed 7, 15, 21 and 30 days after surgery by micro-computed tomography (micro-CT), real-time polymerase chain reaction (RT-PCR) and immunohistochemical analysis. Micro-CT analysis showed that AD had the highest bone volume and the least amount of residual biomaterial at day 30, indicating robust bone formation and efficient resorption. BX + Mg showed significant bone volume but had more residual biomaterial compared to AD. RT-PCR showed that the expression of osteocalcin (OC), the receptor activator of nuclear factor κB (RANK) and sclerostin (SOST), was highest in the AD group at day 21 and vascular endothelial growth factor (VEGF) at day 15, indicating increased osteogenesis and angiogenesis in the AD group. Immunohistochemical staining confirmed intense BMP-2/4 and SMAD-1/5/8 expression in the AD group, indicating osteoinductive properties. The favorable gene expression profile and biocompatibility of AD and BX + Mg make them promising candidates for clinical applications in bone tissue engineering. Further research is required to fully exploit their potential in regenerative surgery.

How Is Bone Regeneration Influenced by Polymer Membranes? Insight into the Histological and Radiological Point of View in the Literature.

The aim of this study was to analyze published works that investigate the in vivo bone regeneration capacity of polymeric membranes loaded with active substances and growth factors. This scoping review's purpose was to highlight the histological and radiological interpretation of the locally produced effects of the polymer membranes studied so far. For the selection of the articles, a search was made in the PubMed and ScienceDirect databases, according to the PRISMA algorithm, for research/clinical trial type studies. The search strategy was represented by the formula "((biodegradable scaffolds AND critical bone defect) OR (polymers AND mechanical properties) OR (3Dmaterials AND cytotoxicity) AND bone tissue regeneration)" for the PubMed database and "((biodegradable scaffolds AND polymers) OR (polymers AND critical bone defects) OR (biodegradable scaffolds AND mechanical properties) AND bone tissue regeneration)" for the ScienceDirect database. Ethical approval was not required. Eligibility criteria included eight clinical studies published between 2018 and 2023. Our analysis showed that polymer membranes that met most histopathological criteria also produced the most remarkable results observed radiologically. The top effective scaffolds were those containing active macromolecules released conditionally and staged. The PLGA and polycaprolactone scaffolds were found in this category; they granted a marked increase in bone density and improvement of osteoinduction. But, regardless of the membrane composition, all membranes implanted in created bone defects induced an inflammatory response in the first phase.

Bone regeneration by a bone substitute biomaterial containing hydroxyapatite, chitosan, xanthan and graphene oxide supplemented with conditioned medium from mesenchymal stem cells.

This study analyzed a recently developed bone substitute biomaterial made of chitosan-xanthanhydroxyapatite-graphene oxide (CXHAG). The CXHAG particles underwent in vitro structural and morphological characterization, and in vivo testing with or without osteogenic conditioned medium from mesenchymal stem cells. Aim: The aim of this study was to determine whether the CXHAG novel biomaterial, supplemented with conditioned medium from mesenchymal stem cells, could be useful for bone regeneration. Materials and Method: For the in vitro study, cells were incubated with 20mg of CXHAG granules for 24 hours and a MTT assay was performed to tests for cytotoxicity. For the in vivo study, critical size calvarial bone defects were created in twenty-five rats. One animal had the defect unfilled (Control Group-CG) and was euthanized after 42 days. Twelve rats received the CXHAG particles (Group 1-G1) and the other twelve received the CXHAG particles supplemented with the conditioned medium (Group 2-G2). All G1/G2 grafts were covered with a CXHAG membrane. G1/G2 animals were euthanized after 14 days (T1) or 42 days (T2). The specimens were processed and histologically evaluated. Results: SEM analysis of the CXHAG particles showed granules of 300-400μm, with a rough irregular surface. They were not cytotoxic to dental pulp stem cells in vitro. The CG specimen showed loose immature connective tissue and no bone formation at the center of the defect. G1 and G2 presented remnant biomaterial particles at both time points, but only G2 had bone formation at the enter of the defect. Conclusions: The conditioned medium had a positive effect on bone regeneration in rat calvarial critical size defects when associated with the novel bone substitute biomaterial.

Converting ocean nacre into bone mineral matrix composite for bone regeneration- in vitro and in vivo studies

Nacre of Pinctada maxima is a natural biomineralized matrix, appeared 7 million years before hominins. In this study, we converted nacre into a self-setting particle bound with multiple calcium orthophosphates that reassemble mammals’ bone mineral matrices for induction of bone regeneration. The nacre-based calcium orthophosphates composite (NCOC) exhibited a compression strength of 10 MPa, which is superior to human trabecular bone. In vitro bioactivity tests revealed the formation of apatite with nano-porous flake-like crystals on the composite surface that mimic HA structure of a human bone matrix. NCOC demonstrated efficient attachment and proliferation of osteoblast cells, promoting osteogenic differentiation by increasing expressions of RUNX2 and OPN. In vivo studies using rabbit back fascia demonstrated that NCOC displays better bone healing and biocompatibility than conventional bone substitute apatite in critical bone defect models. The degradation of calcium carbonate crystal in vivo does not compromise structural integrity of NCOC. Overall, our data showed that NCOC produced through self-setting reactions, presents advantages such as accelerated biodegradation and osteostimulative properties, making it a promising bone substitute for effective bone regeneration.

Advanced 3D printed bone scaffolds with sodium alginate/Tri-calcium phosphate/probiotic bacterial hydroxyapatite: Enhanced mechanical and biocompatible properties for bone tissue engineering

IntroductionThe increasing prevalence of severe bone diseases, such as osteoporosis and critical bone defects, necessitates the development of more effective bone substitutes. This study addresses this need by investigating 3D-printed bone scaffolds composed of sodium alginate and tricalcium phosphate, enhanced with three distinct types of hydroxyapatite (HA): bovine-derived HA, commercially available HA, and HA enriched with probiotic bacteria. We aim to evaluate the performance of these scaffolds in terms of mechanical strength, biocompatibility, and their ability to support bone regeneration. MethodsThe scaffolds were analyzed through various tests, including X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) to characterization. Scanning Electron Microscopy (SEM) was used to examine pore structure, while swelling and degradation tests evaluated the scaffold's stability. Compression testing determined mechanical strength, and in vitro cell culture assays assessed cell proliferation, osteogenic differentiation, and biomineralization. ResultsSEM results indicated that 3D scaffolds with probiotic bacterial HA had the desired 472 μm pore size. These scaffolds demonstrated a strain of 29.26 % and a compressive strength of 10 MPa, meeting the mechanical standards of human trabecular bone. Cell culture studies revealed enhanced cell proliferation by 50 %, osteogenic differentiation with 15.3 U/mg ALP activity, and 1.22-fold biomineralization, suggesting they are highly biocompatible and promote bone growth. ConclusionProbiotic bacterial HA scaffolds exhibit ideal properties and biocompatibility, enhancing bone regeneration and serving as an ideal alternative to chemical types.

Modified Masquelet technique for reconstruction of critical bone defects

Modified Masquelet technique for reconstruction of critical bone defects

Assessment of Novel Surgical Procedures Using Bone Morphogenic Protein-7 Infused Into Decellularised Muscle and Bioactive Ceramic: A Histological Analysis.

Reconstruction of critical bone defects is considered a challenge due to vascular reperfusion injury that may occur. The present study hypothesized that the use of decellularized muscle scaffold (DMS) and bone morphogenic protein-7 (BMP-7), along with resorbable bioactive ceramic silica calcium phosphate cement (SCPC) seeded with human bone marrow stromal cells, can expedite bone formation and maturation. Surgical bone defects were created in 20 nude transgenic mice. In experimental group 1 (n = 10), a critical-size (4mm) calvarial defect was made and grafted with DMS-BMP-7/SCPC. In situ human bone marrow stromal cells [human mesenchymal stromal cells (hMSC)] were seeded thereafter. As a control, group 2 (n = 10) was treated with DMS/SCPC seeded with hMSCs. After 8 weeks, bone regeneration was evaluated using histology and histomorphometry for both groups. Histological examination showed bone regeneration crossing the gap (experimental group 1), bone regeneration was noted at the defect periphery, and scattered islands of bone at the canters of the defects (control group 2). New bone formation and maturation were superior in the groups treated with the DMS/BMP-7/SCPC/hMSC constructs. The quantitative histological assessment revealed that the average bone surface area was 255 ± 25mm2, which was 1.5 times the surface area of group 2, which was reported at 170 ± 35mm2. The reported difference was considered statistically significant (P < 0.05). The DMS-BMP-7/SCPC scaffold induced bone regeneration and neovascularization in critical-size defects.

The management of critical bone defects: outcomes of a systematic approach

BackgroundThe reconstruction of segmental long bone defects remains one of ‘The holy grails of orthopaedics’. The optimal treatment of which remains a topic of great debate. This study aimed to evaluate the outcomes following the management of critical-sized bone defects using a classification-based treatment algorithm.MethodsA retrospective review of all patients undergoing treatment for segmental diaphyseal defects of long bones at a tertiary-level limb reconstruction unit between January 2016 and December 2021, was performed. The management of the bone defect was standardised as per the classification by Ferreira and Tanwar (2020).ResultsA total of 96 patients (mean age 39.8, SD 15.2) with a minimum six months follow-up were included. Most bone defects were the result of open fractures (75/96) with 67% associated with Gustilo-Anderson IIIB injuries. There was a statistical difference in the likelihood of union between treatment strategies with more than 90% of cases undergoing acute shortening and bone transport achieving union and only 72% of cases undergoing the induced membrane technique consolidating (p = 0.049). Of those defects that consolidated, there was no difference in the time to bone union between strategies (p = 0.308) with an overall median time to union 8.33 months (95% CI 7.4 – 9.2 months). The induced membrane technique was associated with a 40% risk of sepsis.ConclusionThis study reported the outcomes of a standardised approach to the management of critical-sized bone defects. Whilst overall results were supportive of this approach, the outcomes associated with the induced membrane technique require further refinement of its indications in the management of critical-sized bone defects.Level of evidence4.

A tetrahedral DNA nanostructure-mediated miRNA inhibitor delivery system: Type H vessel-related bone healing during distraction osteogenesis

The clinical treatment of critical bone defects presents a great challenge, and distraction osteogenesis (DO) emerges as a highly effective strategy. However, prolonged consolidation periods resultant complications limit its clinical applicability. MicroRNA (miR) therapeutic strategies, with a notable focus on miR-205, demonstrate significant potential during DO. Nevertheless, the limited cellular uptake and facile biodegradation of miRNA constrain its applications. To address these challenges, we introduce tetrahedral DNA nanostructure (TDN), an innovative nanomaterial, engineered as gene carriers. TDN delivers the miR-205 inhibitor (TDN@miR205) to synthesize the novel nanoparticles that support bone healing for the first time. TDN@miR205 enhances the osteogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs), whereas TDN alone is ineffective. Further exploration reveals TDN-modulated angiogenesis-osteogenesis communication, establishing a crucial intercellular regulatory mechanism. Notably, TDN@miR205 expedites bone formation by promoting type H vessels-related angiogenesis, secreting SLIT3 to inhibit osteoclasts, inducing SDF1 homing of BMSCs, then upregulating osteogenic genes and proteins via the TGF-β/BMP pathway, facilitating early bony ossification both in vitro and in vivo. In conclusion, TDN@miR205, the multifunctional nanoparticle-mediated vascular bone regeneration significantly contributes to ossification in DO and establishes this platform as a promising and versatile strategy for addressing DO and other complex bone diseases.

Hierarchically porous bone scaffold fabricated via direct foam writing with TCP/ZrO2 composite ink

Customizing bone scaffolds to mimic the hierarchically porous structure of natural bone presents a promising strategy for treating critical bone defects. Although low-cost direct ink writing (DIW) is often used to customize bone scaffolds, the limited print resolution made it difficult to print microporous structures. In this study, DIW was combined with the direct foam method to construct bone scaffolds with hierarchical and interconnected macro-micro porous structures. The foam stabilization mechanism of pure TCP was investigated to prepare TCP-enhanced ZrO2-based composite foam inks. Incorporating TCP endowed a richer interconnection structure to the composite foam. The printed bone scaffolds feature three scales of pore structure: interconnected macropores of 400–500 μm, bubble template pores of 50 μm, and open pores of <20 μm. The scaffold exhibited properties comparable to cancellous bone, such as 90 % porosity, 3.1 MPa compressive strength, and 1.0 GPa elastic modulus. In vitro experiments have demonstrated that cells can grow into the interior of the scaffold by following the connecting pores. And, incorporating TCP significantly enhances osteogenic protein and gene expression in bionic bone scaffolds. This facile and controllable approach offers an alternative solution to addressing the challenge of clinical implant shortages.