Silver nanoparticle technology in orthopaedic infections

The irrational and prolonged use of antibiotics in orthopaedic infections poses a major threat to the development of antimicrobial resistance.To combat antimi-crobial resistance,researchers have implemented various novel and innovative modalities to curb infections.Nanotechnology involves doping ions/metals onto the scaffolds to reach the target site to eradicate the infective foci.In this conno-tation,we reviewed silver nanoparticle technology in terms of mechanism of action,clinical applications,toxicity,and regulatory guidelines to treat ortho-paedic infections.

Autologous peripheral blood-derived orthobiologics:Different types and their effectiveness in managing knee osteoarthritis

Knees are the most commonly impacted weight-bearing joints in osteoarthritis(OA),affecting millions of people worldwide.With increasing life spans and obesity rates,the incidence of knee OA will further increase,leading to a significant increase in the economic burden.Conventional treatment modalities utilized to manage knee OA have limitations.Over the last decade,the role of various autologous peripheral blood-derived orthobiologics(APBOs)for the treatment of knee OA has been extensively investigated.This editorial provided an overview and focused on defining and shedding light on the current state of evidence based on the most recent published clinical studies concerning the use of APBO for the management of knee OA.While numerous studies have demonstrated promising results for these preparations,a notable gap exists in the comparative analysis of these diverse formulations.This absence of head-to-head studies poses a considerable challenge for physicians/surgeons in determining the optimal preparation for managing knee OA and achieving sustained longterm results.Thus,more adequately powered,multicenter,prospective,doubleblind,randomized controlled trials with longer follow-ups are needed to establish the long-term efficacy and to aid physicians/surgeons in determining the optimal APBO for the management of knee OA.

Effect of weight-adjusted antimicrobial antibiotic prophylaxis on postoperative dosage and surgical site infection incidence in total joint arthroplasty

Surgical site infections(SSI)following total joint arthroplasty pose a significant concern for both providers and patients across the globe.Currently,administration of antimicrobial antibiotic prophylaxis is used throughout the world to reduce the incidence of SSI.However,the correct dosage and frequency of administration remains debatable.In this editorial,we emphasized the determination of the effect of administration of weight-adjusted antimicrobial antibiotic prophylaxis regime on the incidence of SSI and postoperative dosage reduction compared to the conventionally used regime during total joint arthroplasty.The results demonstrated similar efficacy between both regimes with respect to the incidence of SSI.In addition,weight-adjustment led to reduced postoperative dosage and has the potential to reduce chances of achieving lower therapeutic concentration,drug resistance,drug toxicity,and costs.

Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

Machine learning and deep neural network-based learning in osteoarthritis knee

Osteoarthritis(OA)of the knee joint is considered the commonest musculoskeletal condition leading to marked disability for patients residing in various regions around the globe.Application of machine learning(ML)in doing research regarding OA has brought about various clinical advances viz,OA being diagnosed at preliminary stages,prediction of chances of development of OA among the population,discovering various phenotypes of OA,calculating the severity in OA structure and also discovering people with slow and fast progression of disease pathology,etc.Various publications are available regarding machine learning methods for the early detection of osteoarthritis.The key features are detected by morphology,molecular architecture,and electrical and mechanical functions.In addition,this particular technique was utilized to assess non-interfering,non-ionizing,and in-vivo techniques using magnetic resonance imaging.ML is being utilized in OA,chiefly with the formulation of large cohorts viz,the OA Initiative,a cohort observational study,the Multicentre Osteoarthritis Study,an observational,prospective longitudinal study and the Cohort Hip&Cohort Knee,an observational cohort prospective study of both hip and knee OA.Though ML has various contributions and enhancing applications,it remains an imminent field with high potential,also with its limitations.Many more studies are to be carried out to find more about the link between machine learning and knee osteoarthritis,which would help in the improvement of making decisions clinically,and expedite the necessary interventions.

Polymethylmethacrylate bone cements and additives: A review of the literature

Polymethylmethacrylate(PMMA) bone cement technology has progressed from industrial Plexiglass administration in the 1950 s to the recent advent of nanoparticle additives. Additives have been trialed to address problems with modern bone cements such as the loosening of prosthesis, high post-operative infection rates, and inflammatory reduction in interface integrity. This review aims to assess current additives used in PMMA bone cements and offer an insight regarding future directions for this biomaterial. Low index(< 15%) vitamin E and low index(< 5 g) antibiotic impregnated additives significantly address infection and inflammatory problems, with only modest reductions in mechanical strength. Chitosan(15% w/w PMMA) and silver(1% w/w PMMA) nanoparticles have strong antibacterial activity with no significant reduction in mechanical strength. Future work on PMMA bone cements should focus on trialing combinations of these additives as this may enhance favourable properties.

Predicting lower limb periprosthetic joint infections: A review of risk factors and their classification

AIM To undertook a systematic review to determine factors that increase a patient's risk of developing lower limb periprosthetic joint infections(PJI).METHODS This systematic review included full-text studies that reviewed risk factors of developing either a hip or knee PJI following a primary arthroplasty published from January 1998 to November 2016. A variety of keywords were used to identify studies through international databases referencing hip arthroplasty, knee arthroplasty, infection, and risk factors. Studies were only included if they included greater than 20 patients in their study cohort, and there was clear documentation of the statistical parameter used; specifically P-value, hazard ratio, relative risk, or/and odds ratio(OR). Furthermore a quality assessment criteria for the individual studies was undertaken to evaluate the presence of record and reporting bias. RESULTS Twenty-seven original studies reviewing risk factors relating to primary total hip and knee arthroplasty infections were included. Four studies(14.8%) reviewed PJI of the hip, 3(11.21%) of the knee, and 20(74.1%) reviewed both joints. Nineteen studies(70.4%) were retrospective and 8(29.6%) prospective. Record bias was identified in the majority of studies(66.7%). The definition of PJI varied amongst the studies but there was a general consensus to define infection by previously validated methods. The most significant risks were the use of preoperative high dose steroids(OR = 21.0, 95%CI: 3.5-127.2, P < 0.001), a BMI above 50(OR = 18.3, P < 0.001), tobacco use(OR = 12.76, 95%CI: 2.47-66.16, P= 0.017), body mass index below 20(OR = 6.00, 95%CI: 1.2-30.9, P = 0.033), diabetes(OR = 5.47, 95%CI: 1.77-16.97, P = 0.003), and coronary artery disease(OR = 5.10, 95%CI: 1.3-19.8, P = 0.017).CONCLUSION We have highlighted the need for the provider to optimise modifiable risk factors, and develop strategies to limit the impact of non-modifiable factors.

Protein tyrosine phosphatases in skeletal development and diseases

Skeletal development and homeostasis in mammals are modulated by finely coordinated processes of migration, proliferation,differentiation, and death of skeletogenic cells originating from the mesoderm and neural crest. Numerous molecular mechanisms are involved in these regulatory processes, one of which is protein posttranslational modifications, particularly protein tyrosine phosphorylation(PYP). PYP occurs mainly through the action of protein tyrosine kinases(PTKs), modifying protein enzymatic activity, changing its cellular localization, and aiding in the assembly or disassembly of protein signaling complexes. Under physiological conditions, PYP is balanced by the coordinated action of PTKs and protein tyrosine phosphatases(PTPs).Dysregulation of PYP can cause genetic, metabolic, developmental, and oncogenic skeletal diseases. Although PYP is a reversible biochemical process, in contrast to PTKs, little is known about how this equilibrium is modulated by PTPs in the skeletal system.Whole-genome sequencing has revealed a large and diverse superfamily of PTP genes(over 100 members) in humans, which can be further divided into cysteine(Cys)-, aspartic acid(Asp)-, and histidine(His)-based PTPs. Here, we review current knowledge about the functions and regulatory mechanisms of 28 PTPs involved in skeletal development and diseases;27 of them belong to class Ⅰ and Ⅱ Cys-based PTPs, and the other is an Asp-based PTP. Recent progress in analyzing animal models that harbor various mutations in these PTPs and future research directions are also discussed. Our literature review indicates that PTPs are as crucial as PTKs in supporting skeletal development and homeostasis.

Is cellular therapy beneficial in management of rotator cuff tears?Meta-analysis of comparative clinical studies

BACKGROUND Mesenchymal stromal cell(MSC)-based cellular therapy promotes type I collagen production,enhance mechanical strength of tissues,and enhance biology at the bone-tendon interface,which primarily explains their potential clinical utility in rotator cuff(RC)tears.AIM To analyze the efficacy and safety of cellular therapy utilizing MSCs in the management of RC tears from clinical studies available in the literature.METHODS We conducted independent and duplicate electronic database searches including PubMed,Embase,Reference Citation Anallysis,Web of Science,and Cochrane Library in August 2021 for studies analyzing the efficacy and safety of cellular therapy(CT)utilizing MSCs in the management of RC tears.Visual Analog Score(VAS)score for pain,American Shoulder and Elbow Surgeons(ASES)score,Disability of the Arm,Shoulder,and Hand score,Constant score,radiological assessment of healing,and complications such as retear rate and adverse events were the outcomes analyzed.Analysis was performed in R-platform using OpenMeta[Analyst]software.RESULTS Six studies involving 238 patients were included for analysis.We noted a significant reduction in VAS score for pain at 3 mo(weighed mean difference[WMD]=-2.234,P<0.001)and 6 mo(WMD=-3.078,P<0.001)with the use of CT,which was not maintained at long-term follow-up(WMD=-0.749,P=0.544).Concerning functional outcomes,utilization of CT produced a significant shortterm improvement in the ASES score(WMD=17.090,P<0.001)and significant benefit in functional scores such as Constant score(WMD=0.833,P=0.760)at long-term follow-up.Moreover,we also observed significantly improved radiological tendon healing during the longterm follow-up(odds ratio[OR]=3.252,P=0.059).We also noted a significant reduction in the retear rate upon utilization of CT in RC tears both at short-(OR=0.079,P=0.032)and long-term(OR=0.434,P=0.027)follow-ups.We did not observe any significant increase in the adverse events directly related to cellular therapy,as compared with the control group(OR=0.876,P=0.869).CONCLUSION Based on our comprehensive and critical review,we could observe that the utilization of CT in RC tear significantly reduced pain severity at 3 and 6 mo,improved short-term functional outcome,enhanced radiological tendon healing,and mitigated retear rates at both short-and long-term follow-ups.The literature also confirmed the relative safety of using MSC therapy in patients presenting with RC tears.

Evidence analysis on the utilization of platelet-rich plasma as an adjuvant in the repair of rotator cuff tears

BACKGROUND Platelet-rich plasma has been gaining popularity as an agent for biological augmentation either as the sole treatment modality or as an adjunct to surgical repair.There is substantial discrepancy in the results of the published meta-analyses;and the true efficacy and role of using autologous platelet-rich plasma(PRP)at the time of rotator cuff repair is still ambiguous.AIM To performed this systematic overview on the overlapping meta-analyses that analyzed autologous PRP as an adjuvant in the repair of rotator cuff tears and identify the studies which provide the current best evidence on this subject and generate recommendations for the same.METHODS We conducted independent and duplicate electronic database searches in PubMed,Web of Science,Scopus,Embase,Cochrane Database of Systematic Reviews,Reference Citation Analysis and the Database of Abstracts of Reviews of Effects on September 8,2021 to identify meta-analyses that analyzed the efficacy of PRP as an adjuvant in the repair of rotator cuff tears.Methodological quality assessment was made using Oxford Levels of Evidence,AMSTAR scoring and AMSTAR 2 grades.We then utilized the Jadad decision algorithm to identify the study with the highest quality to represent the current best evidence to generate the recommendation.RESULTS Twenty meta-analyses fulfilling the eligibility criteria were included.The AMSTAR scores of the included studies varied from 6-10(mean:7.9).All the included studies had critically low reliability in their summary of results due to their methodological flaws according to AMSTAR 2 grades.Significant heterogeneity was observed in the reporting of VAS,function outcome scores(longterm UCLA score,ASES score,SST score),operative time and long-term re-tear rates.Recent metaanalyses are more supportive of the role of intra-operative administration of PRPs at the bonetendon interface in improving the overall healing and re-tear rates,functional outcome and pain.The initial size of the tear and type of repair performed do not seem to affect the benefit of PRPs.Among the different preparations used,leucocyte poor(LP)-PRP possibly offers the greatest benefit as a biological augment in these situations.CONCLUSION Based on this systematic overview,we give a level II recommendation that intra-operative use of PRPs at the bone-tendon interface can augment the healing rate,reduce re-tears,enhance functional outcome and mitigate pain in patients undergoing arthroscopic rotator cuff repair.LPPRP possibly offers the greatest benefit in terms of healing rates,as compared with other platelet preparations.

“Genetic scissors”CRISPR/Cas9 genome editing cutting-edge biocarrier technology for bone and cartilage repair

CRISPR/Cas9 is a revolutionary genome editing technology with the tremendous advantages such as precisely targeting/shearing ability,low cost and convenient operation,becoming an efficient and indispensable tool in biological research.As a disruptive technique,CRISPR/Cas9 genome editing has a great potential to realize a future breakthrough in the clinical bone and cartilage repairing as well.This review highlights the research status of CRISPR/Cas9 system in bone and cartilage repair,illustrates its mechanism for promoting osteogenesis and chondrogenesis,and explores the development tendency of CRISPR/Cas9 in bone and cartilage repair to overcome the current limitations.

Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors.Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+T cells,which led to improved antitumor outcomes.Mechanistically,infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.Overall,we presented a simple,cost-effective,and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.

Sox9基因转染对骨髓间充质干细胞成软骨分化的影响

目的探讨Sox9基因转染对骨髓间充质干细胞（MSCs）成软骨分化的影响。方法采用密度梯度离心和贴壁培养法分离兔骨髓MSCs，体外培养扩增。阳离子脂质体介导重组真核表达Sox9质粒转染骨髓MSCs，通过反转录-聚合酶链反应（RT—PCR）和蛋白印迹实验（Western blot）的方法检测基因产物的表达，荧光显微镜和流式细胞术测定细胞转染效率；四甲基噻唑蓝（MTF）法测定基因转染对细胞增殖能力的影响，流式细胞术对转基因细胞进行细胞周期分析；通过Western blot，RT—PCR和免疫组织化学染色的方法检测Sox9基因转染对MSCs成软骨分化的影响。结果脂质体介导Sox9基因可以成功地转染兔骨髓MSCs；Sox9基因转染对细胞增殖能力无明显影响；基因转染后的细胞表达软骨分化特异性分子Ⅱ型胶原，Sox9，aggrecan等明显增加。结论Sox9基因转染骨髓MSCs可以获得稳定表达，基因表达产物可以促进骨髓MSCs向软骨方向的分化。

Early diagnosis and treatment of acute or subacute spinal epidural hematoma

Background Despite low morbidity, acute or subacute spinal epidural hematoma may develop quickly with a high tendency to paralysis. The delay of diagnosis and therapy often leads to serious consequences. In this study we evaluated the effects of a series of methods for the diagnosis and treatment of the hematoma in 11 patients seen in our hospital. Methods Of the 11 patients （8 males and 3 females）, 2 had the hematoma involving cervical segments, 2 cervico-thoracic, 4 thoracic, 1 thoraco-lumbar, and 2 lumbar. Three patients had quadriplegia, including one with central cord syndrome; another had Brown-Sequard＇s syndrome; and the other seven had paraplegia. Five patients were diagnosed at our hospitals within 3-48 hours after appearance of symptoms, and 6 patients were transferred from community hospitals within 21-106 hours after development of symptoms. Key dermal points, key muscles and the rectal sphincter were determined according to the American Spinal Injury Society Impairment Scales as scale A in two patients, B in 5 and C in 4. Emergency MRI in each patient confirmed that the dura mater was compressed in the spinal canal, with equal intensity or hyperintensity on T1 weighted image and mixed hyperintensity on T2 weighted image. Preventive and curative measures were taken preoperatively and emergency operation was performed in all patients. Open laminoplasty was done at the cervical and cervico-thoracic segments, laminectomy at the thoracic segments, laminectomy with pedicle screw fixation at the thoraco-lumbar and lumbar segments involving multiple levels, and double-sided laminectomy with the integrity of articular processes at the lumbar segments involving only a single level. During the operation, special attention was given to hematoma evacuation, hemostasis and drainage tube placement. Results Neither uncontrollable hemorrhage nor postoperative complications occurred. All patients were followed up for 1-6 years. A marked difference was noted between postoperative and preoperative scales （u=-3.66, P〈0.01）. Most patients recovered after therapy, but the recovery of patients treated at our hospitals was superior to that of those transferred from community hospitals （t =2.95, P〈0.05）. Of the patients treated at our hospitals, 4 were cured and 1 was upgraded with scale from A to D, whereas none of those transferred from community hospitals recovered completely, even one remained scale C. Conclusions Physical examination plus MRI is essential to early diagnosis of acute or subacute spinal epidural hematoma. Preventive and curative measures including emergency operation are helpful to the recovery of patients＇ nerve function.

Surgical treatment for rabbits' femoral arteries subjected to gunshot wounds combining with seawater immersion

Objective: To investigate the surgical treatment methods and evaluate the outcome of gunshot wounds combining with seawater immersion in rabbits’ femoral arteries. Methods: One hundred healthy New Zealand white rabbits (either sex, 3.14 kg± 0.61 kg in weight) were randomly divided into a seawater immersion group (n=50) and a simple injury group (n=50). The unilateral femoral arteries of all the rabbits were injured by 0.38 g steel spheres with velocity of 600-800 m/s fired by a 7.62 mm rifle. The rabbits in the seawater immersion group were immersed in seawater (saline content of 2.54%, pH 8.2- 8.4, and at 21℃) for 60 minutes but those in the simple injury group were not. After the injured segment (observed by naked eyes) of the femoral artery was excised, the blood flow restoration was reconstructed by direct end-to-end anastomosis, reversed autogenous venous grafting or cryopreserved arterial allografting, according to the length of the arterial defects. At 24 hours, and 7, 14 and 21 days after operation, the blood flow was examined. Operative exploration was performed for the animals with partly or fully obstructed blood flow. The tissues around the anastomosis sites and the grafts were harvested for pathological observation under a light microscope and an electron microscope. Results: In the rabbits with completely transected injury, the unobstructed rates in the first 3 weeks after operation were 80.00% in the seawater immersion group and 86.67% in the single injury group, and no significant difference was found between the two groups (P> 0.1). In the rabbits with arterial contusion injury, the unobstructed rates in the first 3 weeks after operation were 86.67% in the seawater immersion group and 82.35% in the single injury group, and no significant difference was found between the two groups (P> 0.1). Most thrombosis occurred in the first operative week. Atypical endothelial cells were detected at the anastomosis sites at the first operative week, and the anastomosis sites were lined with endothelial cells in 3 weeks postoperatively. Conclusions: During the surgical treatment for gunshot wounds combining with seawater immersion, resection of the grossly-injured artery and routine artery reconstruction can obtain satisfactory outcome. Homologous artery is a kind of vascular graft with certain applied value.

全膝关节置换术后的骨溶解：胫骨盘表面的修饰及聚乙烯衬垫灭菌方法对其的影响术 后5至10年的报告

背景：从关节和胫骨假体聚乙烯衬垫后表面转移磨损碎屑，是全膝关节置换术后假体周围骨溶解的主要原因。全膝人工关节假体设计随时问而发生变化，例如对胫骨盘近端表面的粗糙度和聚乙烯衬垫的灭菌方法。我们假设胫骨盘表面抛光和采用空气中γ射线照射之外的其他方法对衬垫灭菌，可降低骨溶解的发生率。方法：从1987年至1998年，我们采用后十字韧带保留型的解剖型组配式全膝人工关节假体系列。对300名患者施行365例全膝关节置换术。术后5至10年，对这些患者的膝关节摄正、侧位X线片。由两位关节置换专家对X线片上的骨溶解状况进行单独评定（骨溶解的界定标准为假体周围存在边缘清晰的非线性松质骨丢失区）。结果：在粗糙表面的胫骨盘的242例膝关节中，使用空气中γ射线照射灭菌的衬垫固定，有34％（82例）骨溶解阳性。用惰性气体中γ射线照射或没有照射的衬垫与抛光表面连接的98例膝关节中，有9％（9例）骨溶解阳性。骨溶解与六项因素相关，这些因素为：一项与患者（男性）相关、一项与胫骨盘（近端表面抛光）相关、三项与聚乙烯衬垫（加工的原材料、灭菌方法及存放时间）相关及一项与手术技术（股骨假体与胫骨假体间的过伸）相关。结论：在这类假体设计中，胫骨盘近端表面采用抛光及衬垫采用更为先进的灭菌方法（不用空气中γ射线照射灭菌）能显著减少骨溶解的发生率，但不能避免骨溶解。

Comparison Study of Corrosion Behavior and Biocompatibility of Polyethyleneimine (PEI)/Heparin and Chitosan/Heparin Coatings on NiTi alloy

Biomedical molecule has received extensive application in surface modification coating.In this paper,polyethyleneimine （PEI）/heparin coating and chitosan/heparin coating on NiTi alloy substrates were prepared by layer-by-layer method,and differences of corrosion behavior and biocompatibility of the coatings were studied.Static contact angles and Fourier transform infrared （FT-IR） test were used to analysis the surface morphology and structure character of the materials,and atomic absorption spectrum was used to verify the corrosion behavior of the materials.Furthermore,hemolysis,dynamic clotting time and platelet binding test were utilized to investigate the biocompatibility of the materials.The results revealed that the blood compatibility of PEI/heparin coating is better than that of the chitosan/heparin coating as well as the substrate.

Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration

It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells(MSCs).However,the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear.This study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on scaffolds.Cyclic mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7,14,or 21 days.At the predetermined time points,culture supernatant was collected for inflammatory mediator detection,and gene expression was analyzed by qRT-PCR.The results showed that the expression of inflammatory mediators(IL1B and IL8)was downregulated(p<0.05)and the expression of ALP(p<0.01)and COL1A1(p<0.05)was upregulated under mechanical loading.The cell-scaffold composites biofabricated with or without mechanical loading were freeze-dried to prepare extracellular matrix-based scaffolds(ECM-based scaffolds).Murine macrophages were seeded on the ECM-based scaffolds to evaluate their polarization.The ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying enhanced the expression of M2 polarization-related biomarkers(Arginase 1 and Mrc1,p<0.05)of macrophages in vitro and increased bone volume/total volume ratio in vivo.Overall,these findings demonstrated that mechanical loading could dually modulate the inflammatory responses and osteogenic differentiation of MSCs.Besides,the ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying facilitated the M2 polarization of macrophages in vitro and bone regeneration in vivo.Mechanical loading may be a promising biofabrication strategy for bone biomaterials.

Time-sequential changes of differentially expressed miRNAs during the process of anterior lumbar interbody fusion using equine bone protein extract, rhBMP-2 and autograft

The precise mechanism of bone regeneration in different bone graft substitutes has been well studied in recent researches. However, miRNAs regulation of the bone formation has been always mysterious. We developed the anterior lumbar interbody fusion （ALIF） model in pigs using equine bone protein extract （BPE）, recombinant human bone morphogenetic protein-2 （rhBMP-2） on an absorbable collagen sponge （ACS）, and autograft as bone graft substitute, respectively. The miRNA and gene expression profiles of different bone graft materials were examined using microarray technology and data analysis, including self-organizing maps, KEGG pathway and Biological process GO analyses. We then jointly analyzed miRNA and mRNA profiles of the bone fusion tissue at different time points respectively. Results showed that miRNAs, including let-7, miR-129, m iR-21, miR-133, miR-140, miR-146, miR-184, and miR-224, were involved in the regulation of the immune and inflammation response, which provided suitable inflammatory microenvironment for bone formation. At late stage, several miRNAs directly regulate SMAD4, Estrogen receptor 1 and 5-hydroxytryptamine （serotonin） receptor 2C for bone formation. It can be concluded that miRNAs play important roles in balancing the inflammation and bone formation.

Biosynthesis of Bioadaptive Materials:A Review on Developing Materials Available for Tissue Adaptation

Biomaterials are increasingly being evolved to actively adapt to the desired microenvironments so as to introduce tissue integration, reconstruct stability, promote regeneration, and avoid immune rejection. The complexity of its mechanisms poses great challenge to current biomimetic synthetic materials. Although still at initial stage, harnessing cells, tissues, or even entire body to synthesize bioadaptive materials is introducing a promising future.