Bone regeneration assisted by synthetic bone substitutes largely depends on the integration of the vascular, neural, and lymphatic systems in the bone. Bone marrow mesenchymal stem cells (BMSCs) are the key cells for this process. However, their role in regulating the integration has not been fully characterized. Human BMSCs (hBMSCs) were treated with osteogenic induction and collected from 0 to 504 h for bulk RNA sequencing (RNA-Seq). Differentially expressed genes (DEGs) were identified and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Time-Series Transcriptomic Trend Analysis were used to comprehensively analyze the possible pathways and functions associated with these DEGs. Weighted Gene Co-expression Network Analysis (WGCNA) was constructed to identify the modules and hub genes of the process. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to validate the expression of key genes identified by RNA-Seq. Time-series analysis of the hBMSCs transcriptome suggested a dynamic expression trajectory during osteogenic differentiation, which was characterized by four functional patterns: the initial adaptation stage (1–24 h), the proliferation activation stage (24–72 h), the differentiation regulation stage (72–336 h) and the remodeling stability stage (336–504 h). Moreover, 72 h was suggested as a potential key time point in the osteogenic–vascular–neural–lymphatic coupling process based on transcriptomic analysis, with typical activation of BMP, vascular endothelial growth factor (VEGF) and PPAR signaling pathways. Four modules and closely related hub genes such as growth differentiation factor 5 (GDF5), matrix Gla protein (MGP) and pregnancy-associated plasma protein A2 (PAPPA2), whose expressions were validated by qRT-PCR and ELISA were also identified and highlighted. Our study revealed the temporal trends of angiogenesis, lymphangiogenesis, and neurogenesis during BMSCs osteogenic differentiation, which not only supplemented the transcriptional regulation in bone regeneration, but also provided a theoretical basis for the design of synthetic bone substitutes.

The repair of multiple organs in motor systems remains a major clinical challenge that necessitates bioactive grafts with a multidirectional differentiation ability. Hydrogel-based organoids implants have emerged as pivotal tools and attracted great attentions. However, strategies to unlock the multipotency of bone marrow mesenchymal stem cells (BMSCs) by precisely modulating the mechanical and structural characteristics of biomimetic extracellular matrix (ECM) during hydrogel-based organoid construction remain underexplored. In this study, a gelatin methacryloyl (GelMA)-based biomimetic ECM mimic hydrogel (HG-2) loaded with BMSCs was developed to construct a multidirectional differentiation organoid, HG-2/3d-BMSC. The hydrogel could provide spatial mechanical stimulation to adherent BMSCs via cell adhesion induced cytoskeleton assembly. RNA sequencing (RNA-Seq) combined with in vitro and in vivo biological experiments reveals that ECM mimic hydrogels deliver adhesion-based spatial mechanical stimulation. This mechanical stimulation specifically unlocks the multipotency of BMSCs during osteogenic differentiation induction. Furthermore, it accelerates and enhances the multidirectional differentiation capacity of BMSCs, simultaneously promoting their commitment to osteogenic, chondrogenic, and tendonogenic tissue lineages. Further investigations prove that adhesion-based spatial mechanical stimulation from the ECM mimic hydrogel enhances multidirectional differentiation of BMSCs-based organoid via Yap/Tead4 (yes-associated protein/TEA domain transcription factor 4) mechanotransduction mediated Kat7 downregulation. The work not only advances the theoretical framework for designing biomaterials that exploit mechanical cues to override biochemical-driven lineage commitment but also establishes a novel paradigm for developing multifunctional organoid constructs to address the clinical challenge of regenerating hierarchically complex tissues in a motor system.

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

Therapeutic ions, such as Si and Mg, play vital roles in regulating metabolism and promoting tissue repair, hence providing an efficient strategy in tissue engineering. The regenerative outcome is strongly dependent on the targeted delivery and controlled release of therapeutic ions. Nevertheless, it remains challenging to deliver multiple ions at controlled manners and ratios. Herein, hierarchical therapeutic ion-based microspheres are fabricated. The coordinated release of Mg and Si ions at pre-set ratios is achieved, based on which, Mg favors osteogenesis by inducing highly efficient cell recruitment and angiogenesis, and Si promotes massive collagen secretion and biomineralization to accelerate the bone maturation process. These therapeutic ion-based microspheres (namely PNM2) can steadily release Mg and Si ions at an optimized ratio of 2:1, which shows the most significant synergistic effect on angiogenesis and osteogenesis. Furthermore, in a rat calvarial defects model, the volume and maturity of the vascularized neo-bone tissue regenerated with PNM2 microspheres are comparable with or even surpassing those defects regenerated with growth factors and/or cell-laden scaffolds. Overall, this platform provides a controllable strategy for the coordinated delivery of Mg/Si ions, opening a new avenue for developing therapeutic ion-based microscaffold for tissue engineering.

Many osteoconductive and osteoinductive scaffolds have been developed for promoting bone regeneration; however, failures would occur in osteogenesis when the defect area is significantly infected while the biomaterials have no antibacterial performances. Herein, a kind of multipurpose PATGP@PDA + Ag microspheres was prepared via emulsion method by using a conductive aniline tetramer (AT) substituted polyphosphazene (PATGP), followed by polydopamine (PDA) modification and silver nanoparticles (AgNPs) loading. The PATGP@PDA + Ag microspheres demonstrated a strong antibacterial activity against Staphylococcus aureus both in vitro and in vivo, while showing no cytotoxicity at an optimized AgNPs loading amount. Due to the electron-donor structure of the AT moieties, the PATGP@PDA + Ag microspheres displayed antioxidant capacities to scavenge reactive oxygen species (ROS). Due to their phosphorus-rich feature, the PATGP@PDA + Ag microspheres favored the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). As controls, nonconductive microspheres (PAGP@PDA, PAGP@PDA + Ag) were prepared similarly by using poly[(ethylalanine)(ethylglycyl)]phosphazene (PAGP). By co-implanting these microspheres with S. aureus into rat calvarial defects, among them, it was determined that the PATGP@PDA + Ag microspheres achieved the most abundant neo-bone formation, benefiting from their antibacterial, antioxidant and osteogenic activities. These results revealed that AgNPs loaded scaffolds made of conductive polyphosphazenes were promising for the regeneration of infected bone defects.

Objective:To explore the long-term clinical efficacy and complications of modified spinous process splitting laminoplasty using coralline hydroxyapatite (SLAC).Methods:The patients who underwent SLAC surgery in this hospital from 2005.5 to 2011.7 were included retrospectively. The perioperative data were collected and followed up. A total of 165 cases were included. Among them, there were 115 males and 50 females; the average age was 56.5±11.4 years (range: 26-84 years), and the average follow-up period was 136.5±23.2 months (range: 108-182 months). The modified Japanese Orthopedic Association (mJOA) score, the neck disability index (NDI) score were used to evaluate the clinical symptoms of patients, and follow-up imaging to observe the changes in cervical spine curvature and mobility.Results:In terms of functional score: mJOA score increased from 11.4±2.9 before surgery to 15.0±1.8 in the early postoperative period but dropped to 14.0±2.5 at the last follow-up ( F=77.096, P<0.001), and NDI score decreased from 19.2%±14.4% before surgery to 13.0%±15.0% in the early postoperative period, but it rose to 14.0%±14.9% at the last follow-up ( F=6.915, P<0.001). The improvement rate of mJOA was 63.5% (early postoperatively) and 50.8% (last follow-up). Regarding the curvature of the cervical spine, the C 2-C 7 Cobb angle decreased from 14.8°±9.1° before surgery to 11.1°±10.5°, and it was maintained at the last follow-up (11.0°±10.1°) ( F=1.083, P=0.342). The cervical spine range of motion decreased significantly, mainly because the Cobb angle in the flexion position decreased from -19.8°±13.6° before the operation to -3.7°±10.6° at the last follow-up ( P<0.001). Seventy-two patients (44.0%) had complications after operation. Six patients (3.6%) developed neurological symptoms aggravated during follow-up, and their mJOA decreased by more than 3 points. 62 patients (37.6%) developed axial symptoms, of which 7 cases were relieved early (within 6 months post-op), 55 patients had persisted symptom and 17 cases (10.3%) remained painful. C 5 nerve root palsy occurred in 10 cases (6.1%) after the operation, 9 cases resolved within two years and the last patient did not resolve. Conclusion:SLAC surgery can effectively alleviate the patient's neurological symptoms and maintain long-term efficacy and cervical lordosis. The occurrence of persistent axial symptoms and the loss of cervical flexion range are long-term complications after SLAC surgery.

There are intensive needs for scaffolds with new designs to meet the diverse requirements of bone repairing. Biodegradable microspheres are highlighted as injectable micro-scaffolds thanks to their advantages in filling irregular defects via a minimally invasive surgery. In this study, microspheres with surface micropores were made via the W1/O/W2 double emulsion method using amphiphilic triblock copolymers (PLLA-PEG-PLLA) composed of poly(L-lactide) (PLLA) and poly(ethylene glycol) (PEG) segments. When the PEG fraction was controlled as 10 wt.%, the microspheres demonstrated higher cell affinity than the smooth-surfaced PLLA microspheres. After being further functionalized with polydopamine coating and apatite deposition, the PLLA-PEG-PLLA microspheres could up-regulate the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) significantly. Before subcutaneous implantation, bone morphogenetic protein-2 (BMP-2) was adsorbed onto the biomineralized microspheres by taking advantages of the strong affinity of apatite to BMP-2. The resulted microspheres induced ectopic osteogenesis efficiently without causing biocompatibility problems. In summary, this study provided a simple strategy to prepare functionalized microspheres with osteoconductivity and osteoinductivity, which showed great potential in promoting bone regeneration as injectable micro-scaffolds.

Current scaffolds applied for bone tissue engineering are still lacking sufficient osteogenic capacity to induce efficient bone regeneration. Biodegradable microsphere-type scaffolds are designed to achieve the dual-controlled release of a Chinese medicine (i.e., icariin, ICA) and a bioactive ion (i.e., Mg2+ ), in order to achieve their synergistic effect on inducing osteogenesis. The hydrophobic icariin is preloaded onto MgO/MgCO3 (1:1 in weight ratio) particles at different amounts and then the particles are encapsulated into biodegradable poly(lactide-co-glycolide) (PLGA) microspheres (PMI) at a fixed fraction (20 wt%). Continuous releases of Mg2+ ion and icariin from the microspheres are detected, showing dependence on icariin amounts. At an optimized moderate loading amount, the resulting PMI-M microspheres display the strongest activation effect on cell biological behaviors among all the designs. By implanting the PMI-M microspheres into rat calvarial defects for 16 weeks, it is found that they can effectively enhance new bone formation, presenting significantly higher capacity in inducing osteogenesis than PMg (containing MgO/MgCO3 but without icariin) and blank PLGA microspheres. Clearly, the released Mg2+ ions are beneficial to osteogenesis, and the coincorporation of icariin exerts supplemental effects in inducing new bone formation, which suggest a promising strategy to regenerate severe bone injuries by designing a dual-release system.

Reactive oxygen species (ROS) are likely to accumulate around severe bone defects, which jeopardizes activities of surrounding cells and hampers new bone formation. An effective strategy to address this issue is to develop scaffolding biomaterials with both antioxidant and osteoinductive capacities. An aniline tetramer (AT) and glycine ethyl ester co-substituted polyorganophosphazene (PATGP) was synthesized, and expected to meet the demands, since the AT moieties were antioxidant and the phosphorus-rich phosphazene moieties were osteocompatible. Moreover, the AT endowed the PATGP with conductivity to match the electrophysiology of bone tissues. By applying in vitro cell culture and in vivo evaluations, microsphere-type scaffolds made of PATGP were systematically characterized on their capacities including ROS-scavenging effect, cytotoxicity and osteoinductivity, using non-conductive poly[(ethylalanato)(ethylglycinato)]phosphazene (PAGP) and poly(lactide-co-glycolide) (PLGA) microspheres as control groups. Among them, PATGP microspheres demonstrated the strongest promotion effects on up-regulating cellular activities and on speeding up neobone formation in rat calvarial defects. Compared to polyester-type biomaterials, in summary, polyorganophosphazenes demonstrated strong flexibility in functionalization by introducing supplementary features such as antioxidant activity and electroactivity, which made them to be quite efficient in enhancing osteogenesis.

目的 比较胸腰椎骨折内固定手术中机器人辅助(robot-assisted,RA)与徒手(free-hand,FH)置入椎弓根螺钉的精度及手术即时效果.方法 采用前瞻性研究,选择我院2015年5月～2020年1月146例椎弓根内固定术,其中65例选择RA螺钉置入(RA组),81例选择FH螺钉置入(FH组).根据Gertzbein与Robbins量表评价椎弓根螺钉置入的准确性,对2组螺钉置入准确性和围手术期指标包括手术时间、术中出血量、疼痛视觉模拟评分(Visual Analogue Scale,VAS)、骨折节段Cobb角、椎体前缘相对高度和是否翻修等进行比较.结果 RA组置入331枚螺钉,其中325枚螺钉A级,5枚B级,1枚C级;FH组置入484枚螺钉,其中431枚螺钉A级,44枚B级,9枚C级.RA组螺钉位置优秀(A级)率明显高于FH组[98.2％(325/331)vs.89.0％(431/484),χ2=24.442,P=0.000].FH组475枚螺钉(98.1％)的位置在临床上是可接受的(A+B级),RA组为330枚(99.7％).RA组手术时间(119.8±38.9)min,显著多于FH组(92.6±25.0)min(t=4.822,P=0.000);术中出血量中位数50.0(25.0,100.0)ml,显著少于FH组100.0(100.0,200.0)ml(Z=-6.261,P=0.000).2组内术后1 d疼痛VAS评分中位数较术前明显降低[RA组:3.0(3.0,3.5)分vs.6.0(6.0,7.0)分,Z=-7.066,P=0.000;FH组:3.0(3.0,4.0)分vs.6.0(6.0,7.0)分,Z=-7.939,P=0.000],但2组间比较差异无显著性(P>0.05).2组内骨折节段Cobb角术后3～5 d较术前明显改善[RA组:9.4° ±3.3°vs.20.3° ±3.8°,t=23.173,P=0.000;FH组:9.7° ±3.4°vs.20.0° ±3.8°,t=23.407,P=0.000],但2组间比较差异无显著性(P>0.05).2组内骨折椎体前缘相对高度出院前较术前明显改善[RA组:(89.2±4.6)％vs.(63.6±4.6)％,t=-174.651,P=0.000;FH组:(89.4±4.9)％vs.(64.1±5.2)％,t=-169.251,P=0.000],但2组间比较差异无显著性(P>0.05).2组患者均未出现手术并发症、术式变更或因手术并发症造成的术后翻修.结论 胸腰椎骨折椎弓根螺钉内固定术中,RA置钉是准确和安全的.

背景:颈椎后纵韧带骨化症(OPLL)在亚洲高发,连续型或混合型OPLL常采用颈椎后路椎板成形术治疗.此类病例中有骨化灶侵及C2或C2以上水平造成脊髓压迫的情况,需进行手术减压.但同时可能破坏颈半棘肌和头半棘肌的肌肉附着点,造成颈椎前凸丢失和术后轴性疼痛.目的:观察保留或重建棘突肌肉附着点的C2椎板穹窿状减压联合棘突纵割式椎板成形术(SLAC)治疗高位颈椎OPLL的临床及影像学疗效.方法:采用回顾性病例系列研究的方法,选取2017年1月至2018年12月在我院因颈椎后纵韧带骨化症且骨化灶压迫侵及C2/3椎间盘水平及以上的手术患者,对该组患者行C2椎板穹隆状减压联合SLAC术.对比术前及末次随访的颈椎JOA评分、颈椎功能障碍指数(NDI)、颈肩痛视觉模拟评分(VAS)、颈椎前凸角等指标,并记录并发症情况.部分患者行术后CT,测量脊髓容纳空间(SAC),并与术前对比,评价影像学效果.结果:共27例患者纳入本研究,其中男21例,女6例,年龄40～81岁,平均(63.9±8.3)岁.随访时间6～20个月,平均(12.9±4.0)个月.与术前比较,末次随访时颈椎JOA评分显著增加(10.8±1.2vs 12.9±1.7,P=0.001),NDI(26.3±6.2 vs 14.4±5.9,P＜0.001)、颈椎前凸角(11.6°±6.9° vs 8.3°±6.2°,P=0.004)显著降低,差异均有统计学意义;但颈肩痛VAS评分(2.4±1.0 vs 2.9±1.3,P=0.131)差异无统计学意义.13例患者术后即刻行CT扫描,手术前后C2水平SAC差异有统计学意义[(6.1±1.9)mm vs (15.3±2.5)mm,P＜0.001].结论:保留或重建棘突肌肉附着点的C2椎板穹窿状减压联合棘突纵割式椎板成形术的临床及影像学结果满意,并不增加术后颈肩部轴性疼痛,可作为治疗高位颈椎后纵韧带骨化症的手术选择.

Hydroxyapatite (HAP) plays an important role in skeleton formation and bone remodeling. Synthetic HAP is similar to naturally occurring HAP and has been widely used in orthopedic and dental implantation. While it is known nano-HAP easily aggregates at high concentrations, the intracellular fate and mechanisms-of-action of dispersed nano-HAP in osteoblast differentiation remain to be fully elucidated. In the present study, we treated the osteoblast cell line MC3T3E1 with autoclaved nano-HAP and added sodium hexametaphosphate to control nanoparticle agglomeration. Dispersed nano-HAP promoted osteoblast differentiation in a dose-dependent manner. Our findings further revealed that the internalized nano-HAP particles were located in typical autophagic vacuoles and increased the ratio of LC3II/LC3I, indicating nano-HAP induced cell autophagy. Moreover, the induction of autophagy by nano-HAP was via mTOR signaling pathway which also concentration dependent. Collectively, these results reveal nano-HAP modulates osteoblast differentiation by mediating autophagy in a dose-dependent manner.

•Functionalized bioresorbable microspheres were prepared via sequential gelatin and apatite coating.•Alendronate was incorporated into the apatite deposition during biomineralization.•Alendronate displayed potentials in activating the osteogenesis-related BMP signaling pathway.•The alendronate-loaded microspheres demonstrated ability in promoting osteogenesis and neovascularization.

目的 探讨骨科机器人辅助技术在颈前路齿状突螺钉内固定手术中的安全性. 方法 2017年11月～2018年8月对9例Ⅱ型齿状突骨折全麻下行齿状突骨折复位,术中三维CT扫描,齿状突螺钉路径规划,骨科机器人引导齿状突螺钉导针植入,齿状突空心螺钉固定. 结果 平均手术时间178.3 min(120～240 min),平均术中估计出血量36.7 ml(20～50ml),术后平均住院时间4.3 d(3～5 d).共置入齿状突螺钉10枚,根据Neo评级量表,10枚螺钉均为0级.所有患者均未发生围手术期并发症.术后3个月随访,所有患者骨折愈合情况良好,无明显骨折不愈合或硬化带形成.Smiley-Webster量表7例优,2例良. 结论 骨科机器人辅助颈椎前路齿状突螺钉内固定术安全、有效,可以作为Ⅱ型齿状突骨折的手术方法.

目的 探讨骨科机器人辅助经皮微创单节段胸腰椎骨折内固定术的学习曲线.方法 选择2015年8月～2017年8月由同一名主任医师连续完成的骨科机器人辅助经皮微创单节段胸腰椎骨折内固定术32例,使用累积和(cumulative sum,CUSUM)方法分析学习曲线,并比较不同阶段手术时间、术中出血量、螺钉置入精度和术后住院时间.结果 所有患者均未发生术中、术后并发症.术后48小时行CT检查,显示螺钉置入位置均可接受,与设计位置偏差0.4～2.1 mm,平均1.16 mm.按手术时间CUSUM学习曲线形态分为3个阶段,前期为病例1～8,中期为病例9～20,后期为病例21～32.3个阶段的手术时间逐渐缩短(P<0.05).螺钉置入偏差在3个阶段的差异具有统计学意义(P=0.027),后期的偏差显著低于前期和中期(P<0.05).术中出血量和术后住院时间在3个时期无明显差异(P=0.685,P=0.057).结论 术者开展8～20例骨科机器人辅助经皮微创单节段胸腰椎骨折内固定术后,能够达到高水平,显著提高手术精度,降低手术时间.

Treatment of infected bone defects still remains a formidable clinical challenge, and the design of bone implants with both anti-bacterial activity and -osteogenesis effects is nowadays regarded as a powerful strategy for infection control and bone healing. In the present study, bioresorbable porous-structured microspheres were fabricated from an amphiphilic block copolymer composed of poly(l-lactide) and poly(ethyl glycol) blocks. After being surface coated with mussel-inspired polydopamine, the microspheres were loaded with nanosilver via the reduction of silver nitrate and apatite via biomineralization in sequence. At optimized loading amounts, the nanosilver-loaded microspheres showed no unfavorable effects on the proliferation and differentiation of bone marrow mesenchymal stem cells despite preserving strong antibacterial activity in in vitro evaluations. For the critical-sized defects (φ = 8 mm) in the rat cranium that was pre-infected with Staphylococcus aureus, the filling of the dual-purpose microspheres demonstrated an effective way to kill bacteria in vivo, and in the meantime, it promoted new bone formation efficiently alongside the degradation of microspheres. Thus, the results suggested that bioresorbable microspheres with both osteoconductive and antibacterial activities were a good choice for treating infected bone defects.

Mineralization capability is an important issue in developing bone repairing biomaterials, while it is not quite clear how this feature would act in the presence of cells and influence cell osteogenic differentiation without adding extra osteoinductive factors such as β‑sodium glycerophosphate and dexamethasone. Poly(l‑lactide) (PLLA) and gelatin composite fibers (PG, 1:1 in weight) were electrospun, treated with CaCl2 solution (PG-Ca), and used for mineralization studies by using cell culture media (αMEM, and αMEM + serum). Bone mesenchymal stromal cells (BMSCs) were then seeded and cultured on both PG and PG-Ca fibrous mats for 28 days by only using αMEM + serum. Interestingly, mineral depositions on both PG and PG-Ca fibers were detected in the environment of αMEM or αMEM + serum, in which, PG-Ca fibers demonstrated stronger ability in inducing hydroxyapatite formation than PG fibers, especially in the presence of fetal bovine serum. When BMSCs were cultured on the two kinds of fibrous mats, apatite depositions were still clearly detected, while the depositing amounts decreased in comparison with corresponding cell-free cases. It was ascribed to the consumption of ions by the continuously proliferating BMSCs, whose osteogenic differentiation was significantly promoted even without extra osteoinductive factors, especially on PG-Ca fibrous mats, in comparison with the control group. Therefore, it was confirmed the capability of scaffolding materials in enriching ions like calcium and phosphate around cells was an efficient way to promote bone regeneration.

目的 比较经椎间孔腰椎椎间融合术(transforaminal lumbar interbody fusion,TLIF)中机器人辅助(robot-assisted,RA)与徒手(free-hand,FH)置入椎弓根螺钉的准确性和安全性.方法 采用前瞻性队列研究的方法,共纳入2016年6月 ～2018年6月TLIF手术116例,由患者选择手术方式,其中RA 57例,FH 59例.比较置钉准确性和围手术期相关指标.根据Gertzbein-Robbins量表和小关节侵犯,评价椎弓根螺钉置入的准确性.围手术期相关指标主要包括手术时间、术中出血量、辐射暴露和是否翻修等.结果 在RA组234枚螺钉中,A级220枚,B级10枚,C级3枚,D级1枚;在FH组的278枚螺钉中,A级244枚,B级20枚,C级10枚,D级2枚,E级2枚.RA组螺钉位置优秀(A级)率高于FH组[94.0％(220/234)vs.87.8％(244/278),χ2=5.837,P=0.016].RA组螺钉的临床可接受(A+B级)率高于FH组[98.3％(230/234)vs.95.0％(264/278),χ2=4.145,P=0.042].RA组螺钉侵犯近端小关节更少[1.7％(4/234)vs.6.5％(18/278),χ2=7.016,P=0.008].RA组辐射剂量更低[(33.3±24.4)μSv vs.(56.8±30.9)μSv,t=-4.563,P=0.000].FH组2枚螺钉需要二次手术翻修,RA组无螺钉需要翻修(P=0.503).结论 与徒手置钉相比,骨科机器人辅助TLIF腰椎置钉具有更高的准确性和安全性.

Biomaterials that have capacities to simultaneously induce bone regeneration and kill bacteria are in demand because bone defects face risks of severe infection in clinical therapy. To meet the demand, multifunctional biodegradable microspheres are fabricated, which contain vancomycin to provide antibacterial activity and strontium-doped apatite to provide osteocompatibility. Moreover, the strontium component shows activity in promoting angiogenesis, which further favors osteogenesis. For producing the microspheres, vancomycin is loaded into mesoporous silica and embedded in polylactide-based microspheres via the double emulsion technique and the strontium-doped apatite is deposited onto the microspheres via biomineralization in strontium-containing simulated body fluid. Sustained release behaviors of both vancomycin and Sr2+ ions are achieved. The microspheres exhibit strong antibacterial effect against Staphylococcus aureus, while demonstrating excellent cell/tissue compatibility. Studies of differentiation confirm that the introduction of strontium element strengthens the angiogenic and osteogenic expressions of mesenchymal stromal cells. Subcutaneous injection of the microspheres into rabbit's back confirms their effectiveness in inducing neovascularization and ectopic osteogenesis. Finally, an infected rabbit femoral condyle defect model is created with S. aureus infection and the multifunctional microspheres are injected, which display significant antibacterial activity in vivo and achieve efficient new bone formation in comparison with biomineralized microspheres without vancomycin loading. The vancomycin- and strontium-loaded microspheres, being biomineralized, injectable, and biodegradable, are attractive because of their flexibility in integrating multiple functions into one design, whose potentials in treating infected bone defects are highly expected.

Magnesium ions (Mg2+) are bioactive and proven to promote bone tissue regeneration, in which the enhancement efficiency is closely related to Mg2+ concentrations. Currently, there are no well-established bone tissue engineering scaffolds that can precisely control Mg2+ release, although this capability could have a marked impact in bone regeneration. Leveraging the power of biodegradable microspheres to control the release of bioactive factors, we developed lactone-based biodegradable microspheres that served as both injectable scaffolds and Mg2+ release system for bone regeneration. The biodegradable microsphere (PMg) was prepared from poly(lactide-co-glycolide) (PLGA) microspheres co-embedded with MgO and MgCO3 at a fixed total loading amount (20 wt%) with different weight ratios (1:0; 3:1; 1:1; 1:3; 0:1). The PMg microspheres demonstrated controlled release of Mg2+ by tuning the MgO/MgCO3 ratios. Specifically, faster release with higher initial concentrations of Mg2+ were detected at higher MgO fractions, while long-term sustained release with lower concentrations of Mg2+ was obtained at higher MgCO3 fractions. All prepared PMg microspheres were non-cytotoxic. Furthermore, they promoted attachment, proliferation, osteogenic differentiation, especially, cell migration of bone marrow mesenchymal stromal cells (BMSCs). Among these microspheres, PMg-III microspheres (MgO/MgCO3 in 1:1) exhibited the strongest promotion of mineral depositions and osteogenic differentiation of BMSCs. PMg-III microspheres were injected into the critical-sized calvarial defect of a rat model, resulting in significant bone regeneration when compared to the control group filled with PLGA microspheres. In the PMg-III group, the new bone volume fraction (BV/TV) and bone mineral density (BMD) reached 32.9 ± 5.6% and 325.7 ± 20.2 mg/cm3, respectively, which were much higher than the values 8.1 ± 2.5% (BV/TV) and 124 ± 35.8 mg/cm3 (BMD) in the PLGA group. These findings indicated that bioresorbable microspheres possessing controlled Mg2+ release features were efficient in treating bone defects and promising for future in vivo applications. STATEMENT OF SIGNIFICANCE: Magnesium plays pivotal roles in regulating osteogenesis, which exhibits concentration-dependent behaviors. However, no generally accepted controlled-release system is reported to correlate Mg2+ concentration with efficient bone regeneration. Biodegradable microspheres with injectability are excellent cell carriers for tissue engineering, moreover, good delivery systems for bioactive factors. By co-embedding magnesium compounds (MgO, MgCO3) with different dissolution rates in various ratios, tunable release of Mg2+ from the microspheres was readily achieved. Accordingly, significant promotion in bone defect regeneration is achieved with microspheres displaying proper sustained release of Mg2+. The developed strategy may serve as valuable guidelines for bone tissue engineering scaffold design, which allows precise control on the release of bioactive metal ions like Mg2+ toward potential clinical translation.