Geometric curvature is a fundamental regulator of cellular functions and bone tissue regeneration, yet its interplay with degradation in biodegradable metals remains elusive due to the insufficient curvature range of existing scaffold design. Here, we introduce additively manufactured Zn-Mg scaffolds inspired by Calabi-Yau manifolds and triply periodic minimal surface, enabling a broad curvature distribution while maintaining consistent pore size and porosity. In vitro, convex regions facilitated Zn ion diffusion and Ca/P mineral deposition, whereas concave regions accumulated Zn ion and suppressed mineral formation. This spatially heterogeneous ion microenvironment reshapes cellular behaviors compared to inert Ti controls. On Ti scaffolds, osteoblasts preferentially migrate toward negatively curved regions due to curvature-driven ECM deformation and focal adhesion signaling. In contrast, on Zn scaffolds, moderate Zn2+ release at convex regions promotes proliferation and mineralization, mediating the intrinsic negative-curvature preference. In vivo, Zn-Mg scaffolds promoted bone regeneration and demonstrated uniform osteointegration compared to Ti controls. These findings reveal curvature-degradation coupling effects and establish architectural design principles for biodegradable metal implants.

Abstract Background Robotic-assisted total joint arthroplasty (rTJA) has witnessed rapid adoption across the Asia-Pacific region. However, practice heterogeneity and conflicting evidence regarding its clinical value necessitate standardized guidance. Therefore, this expert consensus aims to establish consensus-based recommendations to guide and standardize the clinical application of rTJA. Methods The Arthroplasty Society in Asia (ASIA) convened a panel of 45 experts. A modified Delphi technique was employed across three rounds. A systematic literature review informed the generation of consensus statements, which were finalized through anonymous voting. Consensus was defined as ≥ 75% agreement. Results The panel reached consensus on 18 critical clinical questions spanning general principles, total hip arthroplasty, and total knee arthroplasty. Key consensus points include: (1) rTJA demonstrates superior accuracy in implant positioning and alignment restoration compared to manual techniques (98%); (2) current evidence does not yet support a definitive superiority in long-term survivorship or PROMs (77%); (3) robotic platforms are enabling technologies that make personalized alignment philosophies technically reproducible (100%); and (4) soft-tissue balancing should take precedence over rigid mechanical alignment targets in rTKA when conflicts arise(91%). Conclusion This consensus statement provides a comprehensive framework for the application of robotic technology in hip and knee arthroplasty, emphasizing safety, precision, and the need for rigorous training.

Background: LBSA0103 (Synovian ® ) is a high molecular weight single-injection intra-articular hyaluronic acid product crosslinked by 1,4-butanediol diglycidyl ether (BDDE). This randomized, double-blind, multi-center, non-inferiority study was conducted to evaluate the efficacy and safety of this single-injection intra-articular hyaluronic acid (LBSA0103) compared with a three-injection intra-articular hyaluronic acid (Synvisc ® ) in patients with knee osteoarthritis (OA). Methods: 265 patients with knee osteoarthritis were enrolled and randomized to receive three injections of Synvisc ® , or three injections of LBSA0103 (including two sham injections), all at weekly intervals. Patients were followed up at 1 week, 6 weeks, 13 weeks, and 26 weeks after the last injection. The main endpoint was the change of WOMAC-Likert pain score from baseline to 13 weeks after the last injection. The noninferiority was assessed with a margin of 1.6. Other outcome measures were the WOMAC-Likert subscale and total scores; global evaluations by both the patient and investigator; physical examinations; proportion of patients taking rescue medicines; and remission rate in accordance with OMERACT-OARSI standards. Results: The WOMAC-Likert pain scores decreased from baseline to 13 weeks after the last injection with -7.43 and -6.79 respectively for the LBSA0103 and Synvisc groups, indicating a significantly greater decrease in the LBSA0103 group ( p =0.039). The upper limit of 97.5% CI was below the margin of 1.6, confirming the noninferiority of LBSA0103 to Synvisc. The changes of all secondary endpoints at the follow-up visits consistently indicated a general improvement in two groups. Most of them were found no significant differences between the groups, except the changes of WOMAC-Likert pain score, investigator's global assessment and range of motion assessment in the knee from baseline to 26 weeks after the last injection. The safety profile of two groups were comparable and no new safety issue was identified. Conclusions: The single-injection of BDDE-crosslinked LBSA0103 is noninferior to a three injections of Synvisc ® at weekly intervals, providing support that LBSA0103 is a safe and effective option in managing Chinese patients with mild to moderate OA of knee. Trial registration: This study was registered at www.chictr.org.cn with the registration number ChiCTR2400090323 on 27/09/2024.

Titanium and its alloys are widely used for orthopedic implants, but their intrinsic bioinertness may hinder osseointegration. In this study, titanium dioxide nanotube (TNT) arrays were fabricated on Ti-6Al-4V scaffolds via anodization, and their effects on the adhesion behavior of human bone marrow mesenchymal stem cells (hBMSCs) were investigated. Surface characterization showed that anodization successfully generated ordered TNT layers, increased surface roughness, enhanced protein adsorption, and induced an apparent superhydrophilic wetting response. Compared to the untreated scaffold and TNT50, the small-diameter TNT10 surface significantly promoted hBMSC adhesion and proliferation. Microscope imaging further revealed enhanced cell spreading, F-actin organization, and vinculin expression on TNT surfaces, with the most prominent focal adhesion-related staining observed in TNT10. Quantitative proteomic analysis showed that TNT10 was associated with coordinated remodeling of adhesion- and cytoskeleton-related molecular programs, including focal adhesion, cell-substrate junction, and regulation of the actin cytoskeleton. In contrast, TNT50, despite supporting obvious cytoskeletal remodeling, was more compatible with a dynamic, higher-turnover adhesion state. Overall, these findings suggest that small-diameter TNTs provide a more favorable interfacial microenvironment for stable early hBMSC adhesion on porous titanium scaffolds.

Orthopedic implants face persistent clinical challenges of peri-implant infection and impaired osseointegration, especially in high-risk populations with trauma, osteoporosis, or diabetes. Herein, we report a coating-free strategy integrating three-dimensional (3D) printing and electrochemical anodization to fabricate porous titanium alloy implants with TiO2 nanotube (TNT) micro/nano hybrid surfaces. The TNT layer features tunable nanoscale dimensions. In vitro evaluations demonstrate that TNT surfaces exert diameter-dependent biological effects: small-diameter TNTs favor early human bone marrow mesenchymal stem cell (hBMSC) adhesion and proliferation, whereas large-diameter TNTs exhibit the strong antibacterial activity and potent osteogenic differentiation potential. Additionally, TNTs induce transient early M1 macrophage polarization, which synergizes with intrinsic contact-mediated antibacterial activity to accelerate pathogen clearance. Mechanistic investigations reveal that TNTs inhibit Staphylococcus aureus (S. aureus) adhesion and biofilm formation by downregulating topoisomerase I (TopA) to disrupt bacterial DNA topology homeostasis. For osteogenesis, TNTs modulate Filamentous actin (F-actin) cytoskeleton organization and XB130 adaptor protein expression in hBMSCs, thereby activating the PI3K/Akt/GSK3β/β-catenin signaling pathway to drive osteogenic differentiation. In vivo studies using rabbit femoral condyle models confirm that TNT implants exhibit markedly reduced bacterial burden in an infection model and enhanced bone-implant integration. Collectively, these results indicate that TNT 3D-printed titanium implants offer a synergistic platform combining antibacterial defense and enhanced osteointegration. This work provides a mechanistic understanding and preclinical validation for a clinically translatable surface-engineering strategy for next-generation orthopedic implants.

Background Porous metals are characterized by high porosity, which contributes to a low Young’s modulus and facilitates new bone tissue ingrowth and fluid exchange. Titanium and tantalum are the most widely used porous metals in orthopaedics. Although many studies have compared porous titanium and porous tantalum, their findings remain inconsistent. This study aimed to compare the biological functions of porous titanium and porous tantalum and provide recommendations for clinical decision-making. Methods A systematic review and meta-analysis were conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. After retrieval and screening, 38 relevant studies on porous titanium and porous tantalum were included. We categorized all research results into four outcome measures: biocompatibility, osteogenic characteristics, biomechanical characteristics, and bacterial adhesion properties, conducting quantitative meta-analysis or qualitative assessment. The implantation sites covered multiple regions, including the cervical vertebra, lumbar vertebra, femur, hip joint, and others. Results The meta-analysis revealed no statistically significant differences between porous titanium and porous tantalum in terms of biocompatibility, osteogenic characteristics, and biomechanical characteristics at the cellular, animal, and clinical levels (all P > 0.05). Qualitative assessment of bacterial adhesion properties also revealed no major differences between the two materials. Conclusions This systematic review and meta-analysis suggest that porous titanium and porous tantalum lack statistically significant differences in biological functions. In view of the lower weight, reduced cost, and broad clinical adoption of porous titanium, it is recommended as the preferred option in the absence of clear advantages from porous tantalum.

Background:The use of porous metal acetabular components combined with augments is a potential approach for revision hip arthroplasty in cases of severe bone defects. However, the strength of the augment-acetabular cup interface has not been studied previously. This study evaluated the interfacial strength between acetabular cups and augments. Methods:The strength of the interface between the augment, bone cement, and the acetabular cup was tested using lever-out test. The effects of contact area and type of bone cement on the interface strength were investigated. Results:The interfaces exhibited excellent stability. With the same cup-augment combination and different bone cements with different properties, no statistical differences were observed in main mechanical indicators (p > 0.05); however, when the same bone cement was used with different cup-augment combinations, the maximum moment and yield moment decreased significantly with a decrease in the contact area (p < 0.05). The interface stiffness exhibited a decreasing trend, although the difference was not statistically significant. Failure always occurred on the cement-acetabular cup side. Conclusion:The interface between the acetabular cup and augment is stable and primarily influenced by the size of the contact area, not the type and mechanical properties of bone cement. Clinical Relevance:This study provides a theoretical basis for the use of augments during revision surgery. The factors affecting the strength were explored. This could promote the improvement of prostheses and guide the design of a new generation of prostheses.

Long-distance running is not a recommended form of exercise after total hip arthroplasty (THA). However, younger and more active patients often wish to return to sport after THA. We present the case of a 38-year-old man who underwent bilateral THA for osteonecrosis. Three months after surgery and rehabilitation, the patient returned to his normal life. He returned to sport one year after surgery when he engaged in long-distance running and documented his daily exercise status. In the fourth year after surgery, he completed a full marathon race with a total length of 42.2km. Magnetic resonance imaging of the bilateral hip joints performed within 48 hours after the marathon revealed no oedema in the greater trochanteric region and a small amount of fluid accumulation in the hip joints. Bilateral THA achieved excellent clinical and radiographic results based on clinical manifestations and magnetic resonance imaging. Keywords: Total hip arthroplasty; Magnetic resonance imaging; Long-distance running; Return to sport.

We prepared Zn/Poly(lactic acid) (PLA) composite films for guiding bone regeneration. The surface of Zn foil was modified by micro-arc oxidation, and the composite films with a sandwich structure were prepared using hot pressing method. The morphology, roughness, porosity, and pore size of Zn foil were investigated with the help of laser microscope and SEM. As a result, the rough and porous surface with the Sa value of 2.764+0.071 mu m and porosity of 12.5+3.2 % provided a favorable structural basis for subsequent combination between Zn foil and PLA. While the value of Sa for the MAO-Zn/PLA40 composite film was 4.510+0.080 mu m. The main component of the oxide layer was ZnO according to the XRD and XPS results. The tensile strength of MAO-Zn/PLA40 composite film increased by 17.7+0.6 % compared with that of Zn/PLA40 composite film. The interface energy decreased from-7.074 kcal/mol for Zn/PLA to-1433.430 kcal/mol for ZnO/PLA and the total energy level of ZnO/PLA composites shifted towards lower direction according to the density of state results. These results illustrated the enhanced interfacial bonding effect between the micro-arc oxide layer and PLA based on mechanical interlocking and electrostatic attraction. Additionally, micro-arc oxidation accelerated the degradation of Zn foil from initial 0.383+0.029 mm/year to 1.245+0.208 mm/year according to the electrochemical performances. This investigation provided an experimental basis and theoretical guidance for regulating the mechanical properties and degradation rate of this kind of membrane.

ObjectiveA robotic system was recently introduced to improve prosthetic alignment during total knee arthroplasty (TKA). The purpose of this multicenter, prospective, randomized controlled trial (RCT) was to determine whether robotic‐arm‐assisted TKA improves clinical and radiological outcomes when compared to conventional TKA.MethodsOne hundred and thirty patients who underwent primary TKA were enrolled in this prospective, randomized controlled trial, which was conducted at three hospitals. Five patients were lost to follow‐up 6 weeks after surgery. Therefore, 125 participants (63 in the intervention group and 62 in the control group) remained in the final analysis. The primary outcome was the rate at which the mechanical axis of the femur deviated by less than 3° from the mechanical axis of the tibia. This was evaluated by full‐length weight‐bearing X‐rays of the lower limb 6 weeks postoperatively. Secondary outcomes included operation times, 6‐week postoperative functional outcomes evaluated by the American Knee Society score (KSS) and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), short form‐36 (SF‐36) health survey results, and the occurrence of adverse events (AEs) and serious adverse events (SAEs).ResultsAt 6 weeks postoperatively, we found that the rate of radiographic inliers was significantly higher in the intervention group (78.7% vs 51.6%; p = 0.00; 95% confidence interval, 10.9% to 43.2%). The operation was significantly longer in the intervention group than in the control group (119.5 vs 85.0 min; p = 0.00). There were no significant differences in the 6‐week postoperative functional outcomes, SF‐36, AEs, and SAEs between the two groups. There were no AEs or SAEs that were determined to be “positively related” to the robotic system.ConclusionRobotic‐arm‐assisted TKA is safe and effective, as demonstrated in this trial.

OBJECTIVE:Total hip arthroplasty (THA) is currently one of the most effective treatment methods for end-stage hip joint disease, and its long-term effectiveness largely depends on the accurate placement of the acetabular prosthesis. In conventional surgery, the placement of the acetabular prosthesis mainly relies on the surgeon's clinical experience and surgical techniques. To further improve the accuracy of prosthesis placement, a new robotic system for THA is designed. The purpose of this study is to verify the effectiveness and safety of THA assisted by this robotic system. METHOD:A multicenter, prospective, randomized controlled, superiority study design was adopted with statistical methods of t test and Chi-squared test. Participants undergoing primary THA have been enrolled in three centers of joint surgery in China since July 17, 2023. Robotic THA was operated in the experimental group, and conventional instruments were used in the control group. The primary outcome is the proportion of anteversion and inclination angles in the safe zone. The secondary outcomes include operation time, WOMAC score, Harris score, SF-36 health questionnaire, dislocation rate of hip joint, and rates of adverse events and serious adverse events. RESULTS:A total of 138 patients were included in this study. The proportion of both anteversion and inclination angles in the safe zone was 92.2% in the experimental group and 50.8% in the control group, with significant difference (p < 0.01). The average operation time in the experimental group and control group was 116.4 and 80.5 min respectively, with significant difference (p < 0.01). There was no significant difference in WOMAC score, Harris score, and SF-36 between the two groups (6 ± 2) weeks after operation (p > 0.05). The dislocation rate of hip joint in the experimental group and control group were 3.0% and 1.5%, respectively, without significant difference (p > 0.05). The rate of adverse events and severe adverse events in the experimental group and control group also showed no significant difference (p > 0.05). No adverse events or serious adverse events were judged to be "definitely related" to the experimental instruments. CONCLUSION:Robotic THA could prolong the operation time within an acceptable range, but more precise acetabular prosthesis positioning could be obtained when compared with conventional surgery. Besides, no significant difference was found in function scores, dislocation rate or other adverse events, which indicates that this new robot system shows both good effectiveness and safety in THA. TRIAL REGISTRATION:Clinical Trials: NCT05947734.

The three-dimensional-printed Ti6Al4V implant (3DTi) has been widely accepted for the reconstruction of massive bone defects in orthopedics owing to several advantages, such as its tailored shape design, avoiding bone graft and superior bone-implant interlock. However, the osteoinduction activity of 3DTi is inadequate when applied clinically even though it exhibits osteoconduction. This study developes a comprehensive coatless strategy for the surface improvement of 3DTi through copper (Cu) ion implantation and ultraviolet (UV) photofunctionalization to enhance osteoinductivity. The newly constructed functional 3DTi (UV/Ti-Cu) achieved stable and controllable Cu doping, sustained Cu2+ releasing, and increased surface hydrophilicity. By performing cellular experiments, we determined that the safe dose range of Cu ion implantation was less than 5x1016 ions/ cm2. The implanted Cu2+ enhanced the ALP activity and the apatite formation ability of bone marrow stromal cells (BMSCs) while slightly decreasing proliferation ability. When combined with UV photofunctionalization, cell adhesion and proliferation were significantly promoted and bone mineralization was further increased. Meanwhile, UV/Ti-Cu was conducive to the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro, theoretically facilitating vascular coupling osteogenesis. In conclusion, UV/Ti-Cu is a novel attempt to apply two coatless techniques for the surface modification of 3DTi. In addition, it is considered a potential bone substrate for repairing bone defects.

[This corrects the article DOI: 10.1016/j.bioactmat.2023.11.001.].

Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A three-dimensional (3D)-printed porous Ti6Al4V scaffold (3DTi) is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants, including a lower elasticity modulus, stronger bone-implant interlock, and larger drug-loading space. Simvastatin is a multitarget drug with anti-tumor and osteogenic potential; however, its efficiency is unsatisfactory when delivered systematically. Here, simvastatin was loaded into a 3DTi using a thermosensitive poly (lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and osteogenic effects. Newly constructed simvastatin/hydrogel-loaded 3DTi (Sim-3DTi) was comprehensively appraised, and its newfound anti-osteosarcoma mechanism was explained. Specifically, in a bone defect model of rabbit condyles, Sim-3DTi exhibited enhanced osteogenesis, bone in-growth, and osseointegration compared with 3DTi alone, with greater bone morphogenetic protein 2 expression. In our nude mice model, simvastatin loading reduced tumor volume by 59%-77 % without organic damage, implying good anti-osteosarcoma activity and biosafety. Furthermore, Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both in vivo and in vitro. Sim-3DTi is a promising osteogenic bone substitute for osteosarcoma-related bone defects, with a ferroptosis-mediated anti-osteosarcoma effect.

Abnormal retro patellar stress is believed to contribute to patellofemoral complications after total knee arthroplasty (TKA), but the causal link between TKA and patellofemoral contact stress remains unclear. By reviewing the relevant studies, we found that both TKA implantation and additional patellar resurfacing increase retro patellar pressure. The rotation and size of the femoral component, thickness and position of the patellar component, installation of the tibial component, prosthesis design and soft tissue balance further influence patellofemoral stress. Specific measures can be applied to reduce stress, including the installation of the femoral prosthesis with an appropriate external rotation angle, placing the tibial component at a more posterior position and the patellar button at a more medial position, avoiding over-sized femoral and patellar components, selecting posterior-stabilized design rather than cruciate-retaining design, using gender-specific prosthesis or mobile-bearing TKA system, and releasing the lateral retinaculum or performing partial lateral facetectomy. Despite these measures, the principle of individualization should be followed to optimize the patellofemoral biomechanics.

Objective: To analyse the proximal femoral morphology on three-dimensional reconstructed imagery to explore the factors influencing the relevant parameters. Method: The cross-sectional study was conducted at Peking University Third Hospital in northern China from January 2019 to August 2020, and comprised healthy adults who underwent computed tomography scanning. Three-dimensional computed tomography reconstruction of the proximal femoral medullary cavity was performed using Mimics 22. The anatomical parameters related to total hip arthroplasty were measured to examine the relationship among gender, age and femoral length. Data was analysed using SPSS 20. Results: Of the 63 adults, meaning 126 hips, 21(33.3%) were males, meaning 42(33.3%) hips, and 42(66.6%) were females, meaning 84(66.6%) hips. The overall mean age was 51.5±23.1 years (range: 23-68 years). The inflection point of the medullary cavity curved at 5-10mm distal to the lesser trochanteric line. Most horizontal plane parameters significantly differed between men and women (p<0.05), with the mean medullary cavity being wider in men than women. There was a significant difference between the genders in the sagittal anterior-posterior diameter of the canal flare index (p<0.05). Age was negatively correlated with the coronal medial-lateral diameter and coronal lateral diameter of canal flare index. In the coronal and sagittal planes, there was a positive correlation between the metaphysis and diaphysis, and the coronal and sagittal planes were positively correlated with the orthogonal plane. Conclusions: Femoral morphology could be influenced by gender and age. Morphological changes of the proximal femoral medullary cavity were not present in a single plane, but were affected by multiple planes. When the diameter of one plane became larger, its orthogonal plane concomitantly increased. Key Words: Proximal femoral, Morphology, CT measurement, Correlation.

Osteosarcoma is a malignant bone tumor occurring in adolescents. Surgery combined with adjuvant or neoadjuvant chemotherapy is the standard treatment. However, systemic chemotherapy is associated with serious side effects and a high risk of postoperative tumor recurrence, leading to a high amputation rate and mortality in cancer patients. Implant materials that can simultaneously repair large bone defects and prevent osteosarcoma recurrence are in urgent need. Herein, an intelligent system comprising 3D-printed titanium scaffold (TS) and pH-responsive PEGylated paclitaxel prodrugs was fabricated for bone defect reconstruction and recurrence prevention following osteosarcoma surgery. The drug-loaded implants exhibited excellent stability and biocompatibility for supporting the activity of bone stem cells under normal body fluid conditions and the rapid release of drugs in response to faintly acidic environments. An in vitro study demonstrated that five human osteosarcoma cell lines could be efficiently eradicated by paclitaxel released in an acidic microenvironment. Using mice models, we demonstrated that the drug-loaded TS can enable a pH-responsive treatment of postoperative tumors and effectively prevent osteosarcoma recurrence. Therefore, local implantation of this composite scaffold may be a promising topical therapeutic method to prevent osteosarcoma recurrence.

Background: Porous metal augments are used in complex hip arthroplasty; however, few studies have assessed their efficacy and safety. This systematic review analyzed the use of augments in revision hip arthroplasty and summarized the clinical research findings.Methods: We used combinations of "revision," "replacement," "arthroplasty," "augment," "acetabular," and "hip" to search PubMed, Web of Science, EMBASE, Cochrane Library databases, and clinical trial registration platform "Clinicaltrials" for relevant literature. The functional score, restoration of hip center of rotation, revision of implants, and complications were analyzed. Patients were divided into 3 subgroups according to the mean follow-up period. Overall, 19 reports involving 647 patients (655 hips) were selected. The mean age at the time of surgery was 63 years (range, 24-106) and the mean follow-up duration was 66 months (range, 11-204). Results: Harris Hip Score increased from approximately a mean of 40 points preoperatively to a mean of 84 points postoperatively. The vertical distance between hip center of rotation and teardrop was restored from a preoperative distance of 41.9 to 21.7 mm postoperatively. The overall acetabular revision rate was 4.7%, and the incidence of complications was 8.2%. There were significant differences in the reoperation, acetabular revision, and complication rates among the subgroups.Conclusion: Metal augments used in revision hip arthroplasty are a safe and effective treatment option to correct acetabular defects. (c) 2022 Elsevier Inc. All rights reserved.

Background: Three-dimensional (3D) printing technology has been widely used in orthopedics; however, it is still limited to the change of macroscopic structures. In order to further improve the biological properties of 3D-printed porous titanium scaffolds, this study introduced micro-arc oxidation (MAO) technology to modify the surface of porous titanium scaffolds and construct bioactive coatings on the surface of porous titanium scaffolds to improve the biocompatibility and osseointegration ability of the material. Methods: For in vitro experiments, human bone marrow stem cells (hBMSCs) were seeded onto untreated scaffolds (control group) and MAO-treated scaffolds (experimental group). After 24 h of co-culture, cytotoxicity was observed using live/dead staining, and cell/scaffold constructs were retrieved and processed for the assessment of cell morphology by using scanning electron microscopy (SEM). Cell proliferation was detected using the Cell Counting Kit-8 (CCK-8) assay after 3, 7, and 14 days of co-culture. The levels of alkaline phosphatase (ALP) in the cell supernatant were detected after 7 and 14 days of co-culture. For in vivo experiments, micro-computed tomography (micro-CT) and Masson Goldner's staining were used to evaluate bone ingrowth and osseointegration at 4 and 8 weeks postoperatively. Results: In vitro experiment results confirmed that the two groups of scaffolds were non-cytotoxic and the cell adhesion status on the MAO-treated scaffolds was better. Over time, cell proliferation and ALP levels were higher in the MAO-treated group than in the untreated scaffolds. In the in vivo experiments, the MAO-treated scaffolds showed better bone ingrowth and osseointegration than the untreated group at different time points. Conclusions: The MAO-treated porous titanium scaffold formed a uniform and dense bioactive coating on the surface, which was more conducive to cell adhesion, proliferation, and differentiation and showed better osseointegration and bone ingrowth in vivo.

Significant efforts on construction of smart drug delivery for developing minimally invasive gelling system to prolong local delivery of bisphosphonates are considered as promising perspectives for the bone-related diseases, which provide the hydrogels with unique bioactivities for bone repair in clinic. Herein, we have constructed an alendronate (ALN)-conjoined injectable tetra-PEG hydrogel with excellent biocompatibility, uniform network, and favorable mechanical properties in one-pot strategy. In views of the quick ammonolysis reaction between N-hydroxysuccinimide (NHS)-ester of tetra-PEG-SG and amine groups of tetra-PEG-NH2 polymer and ALN molecules, the uniform networks were formed within seconds along with the easy injection, favorable biocompatibility and mechanical properties for hydrogel scaffolds. On account of the simultaneous physical encapsulation and chemical linkage of the ALN within the hydrogels, the ALN-conjoined tetra-PEG hydrogel exhibited a sustained drug release delivery that could persistently and effectively facilitate viability, growth, proliferation, and osteogenesis differentiation of stem cells, thereby allowing the consequent adaptation of hydrogels into the bone defects with irregular shapes, which endowed the ALN-conjoined tetra-PEG hydrogel with depot formulation capacity for governing the on-demand release of ALN drugs. Consequently, the findings imply that these drug-based tetra-PEG hydrogels mediate optimal release of therapeutic cargoes and effective promotion of in situ bone regeneration, which will be broadly utilized as therapeutic scaffolds in tissue engineering and regenerative medicine.