Three-dimensional (3D) bioprinting has revolutionized tissue engineering by precisely fabricating customized scaffolds that recapitulate native tissue architectures. This study introduces a photo-crosslinkable methacrylated guar gum (GG-MA) hydrogel as a tunable monophasic bioink for cartilage tissue engineering. By adjusting methacrylation degrees, GG-MA hydrogels achieved tailored mechanical strength (Young’s modulus: GG-MA2 = 0.184 MPa vs. GG-MA1 = 0.069 MPa), controlled degradation (61.41

Introduction:Orthopedic implant failure due to inadequate osseointegration and infection remains a critical challenge. To address this, we engineered a polydopamine (PDA)-mediated dual-functional platform for lithium (Li+) and copper (Cu2+) co-incorporation on titanium alloy (Ti6Al4V) implants, aiming to synergize osteogenic and antibacterial properties through a scalable surface modification strategy. Methods:PDA coatings were polymerized onto polished Ti64 substrates, followed by sequential immersion in LiCl (800 μM) and CuCl2 (10 μM) solutions to construct Li+/Cu2+ co-doped surfaces (PDA@Li 800-Cu 10). In vitro assays assessed MC3T3-E1 pre-osteoblast proliferation (CCK-8), osteogenic differentiation (ALP activity, RT-PCR for ALP/Axin2), and antibacterial activity against S. aureus and E. coli (live/dead staining, CFU assays). In vivo efficacy was evaluated in a rat femoral defect model via micro-CT and histology. Results and discussion:Li+-functionalized surfaces (PDA@Li 800) enhanced osteoblast proliferation and osteogenesis via Wnt/β-catenin activation. Cu2+-loaded coatings (PDA@Cu 10) eradicated >99% bacteria but moderately suppressed osteogenic markers. The dual-doped PDA@Li 800-Cu 10 surface resolved this bioactivity conflict, maintaining antibacterial efficacy comparable to PDA@Cu 10 while elevating the osteogenic capacity of Cu2+-only modified surfaces. In vivo, dual-modified implants eliminated bacterial colonization within 72 h and significantly increased peri-implant bone volume (BV/TV) in comparison to Ti64 controls, outperforming PDA-only counterparts. By harmonizing Li-driven osteoinduction and Cu-mediated bactericidal action through a scalable PDA platform, this work advances a transformative strategy for next-generation orthopedic and dental implants, simultaneously addressing infection risks and bone regeneration demands.

Infection is the most prevalent complication of fractures, particularly in open fractures, and often leads to severe consequences. The emergence of bacterial resistance has significantly exacerbated the burden of infection in clinical practice, making infection control a significant treatment challenge for infectious bone defects. The implantation of a structural stent is necessary to treat large bone defects despite the increased risk of infection. Therefore, there is a need for the development of novel antibacterial therapies. The advancement in antibacterial biomaterials and new antimicrobial drugs offers fresh perspectives on antibacterial treatment. Although antimicrobial 3D scaffolds are currently under intense research focus, relying solely on material properties or antibiotic action remains insufficient. Antimicrobial peptides (AMPs) are one of the most promising new antibacterial therapy approaches. This review discusses the underlying mechanisms behind infectious bone defects and presents research findings on antimicrobial peptides, specifically emphasizing their mechanisms and optimization strategies. We also explore the potential prospects of utilizing antimicrobial peptides in treating infectious bone defects. Furthermore, we propose that artificial intelligence (AI) algorithms can be utilized for predicting the pharmacokinetic properties of AMPs, including absorption, distribution, metabolism, and excretion, and by combining information from genomics, proteomics, metabolomics, and clinical studies with computational models driven by machine learning algorithms, scientists can gain a comprehensive understanding of AMPs' mechanisms of action, therapeutic potential, and optimizing treatment strategies tailored to individual patients, and through interdisciplinary collaborations between computer scientists, biologists, and clinicians, the full potential of AI in accelerating the discovery and development of novel AMPs will be realized. Besides, with the continuous advancements in 3D/4D/5D/6D technology and its integration into bone scaffold materials, we anticipate remarkable progress in the field of regenerative medicine. This review summarizes relevant research on the optimal future for the treatment of infectious bone defects, provides guidance for future novel treatment strategies combining multi-dimensional printing with new antimicrobial agents, and provides a novel and effective solution to the current challenges in the field of bone regeneration.

The technology of three dimensional (3D) printing, also known as additive manufacturing, is a cutting-edge type of fabrication method that utilizes a computer-aided design platform and employs layer-by-layer stacking to construct objects with exceptional flexibility. Due to its capacity to produce a substantial quantity of products within a short period of time, 3D printing has emerged as one of the most significant manufacturing technology. Over the past two decades, remarkable advancements have been made in the application of 3D printing technology in the realm of bone tissue engineering. This review presents an innovative and systematic discussion on the potential application of 3D printing technology in bone tissue engineering, particularly in the treatment of infected bone defects. It comprehensively evaluates the materials utilized in 3D printing, highlights the interplay between cells and bone regeneration, and addresses and resolves challenges associated with current 3D printing technology. These challenges include material selection, fabrication of intricate 3D structures, integration of different cell types, streamlining design processes and material selection procedures, enhancing the clinical translational potential of 3D printing technology, and ultimately exploring future applications of four dimensional (4D) printing technology. The 3D printing technology has demonstrated significant potential in the synthesis of bone substitutes, offering consistent mechanical properties and ease of use. It has found extensive applications in personalized implant customization, prosthetic limb manufacturing, surgical tool production, tissue engineering, biological modeling, and cell diagnostics. Simultaneously, 3D bioprinting provides an effective solution to address the issue of organ donor shortage. However, challenges still exist in material selection, management of structural complexity, integration of different cell types, and construction of functionally mature tissues. With advancements in multi-material printing techniques as well as bioprinting and 4D printing technologies emerging on the horizon; 3D printing holds immense prospects for revolutionizing the means by which infectious bone defects are repaired.

Bacterial-infected skin wounds caused by trauma remain a significant challenge in modern medicine. Clinically, there is a growing demand for wound dressings with exceptional antibacterial activity and robust regenerative properties. To address the need, this study proposes a novel multifunctional dressing designed to combine efficient gas exchange, effective microbial barriers, and precise drug delivery capabilities, thereby promoting cell proliferation and accelerating wound healing. This work reports the development of a 3D-printed hydrogel scaffold incorporating flavanone (FLA)-loaded ZIF-8 nanoparticles (FLA@ZIF-8 NPs) within a composite matrix of κ-carrageenan (KC) and konjac glucomannan (KGM). The scaffold forms a stable dual-network structure through the chelation of KC with potassium ions and intermolecular hydrogen bonding between KC and KGM. This dual-network structure not only enhances the mechanical stability of the scaffold but also improves its adaptability to complex wound environments. In mildly acidic wound conditions, FLA@ZIF-8 NPs release Zn2+ and flavanone in a controlled manner, providing sustained antibacterial effects and promoting wound healing. In vivo studies using a rat full-thickness infected wound model demonstrated that the FLA@ZIF-8/KC@KGM hydrogel scaffold significantly accelerated wound healing, showcasing its superior performance in the treatment of infected wounds.

Low back pain is among the most grave public health concerns worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The destruction of annulus fibrosus (AF) is the primary cause of IVDD. A sustainable and stable treatment system for IVDD is lacking because of the special organizational structure and low nutrient supply of AF. We here found that IVDD results in the impaired mitochondrial function of AF tissue, and mitochondrial autophagy (mitophagy) plays a protective role in this process. We therefore reported a thread-structural microneedle (T-MN) matching the ring structure of AF. Based on the adsorption effect of laminin, our T-MN could load with bone marrow mesenchymal stem cell-derived exosomes to envelope the regulating mitophagy microRNA (miRNA 378), named as T-MN@EXO@miR-378. In general, we offered in situ locking in the defect site of AF to prevent nucleus pulposus leakage and promoted AF repair. The design of the thread structure was aimed at bionically matching the layered AF structure, thereby providing stronger adhesion. The T-MN@EXO@miR-378 effectively attached to AF and slowly released therapeutic engineered exosomes, and prevented IVDD progression by restoring mitophagy, promoting AF cell proliferation and migration, and inhibiting the pathological remodeling of the extracellular matrix. This functional system can be used as an excellent tool for sustained drug release and has a certain prospect in substituting the conventional treatment of IVDD.

Implant osseointegration is a complex physiological process that requires spatial and temporal regulation of immune response and osteogenesis. It is vital to find effective therapeutic strategies to regulate the immune microenvironment of bone defects and further promote osteogenesis. In this study, we prepared high performance Zn-Mn-Li alloys and deposited CaP coatings on the surface of Zn-Mn-Li scaffolds by phosphate chemical conversion (PCC) technology. Based on the strategy of bone immune regulation, the influence of immune microenvironment formed by Zn-Mn-Li scaffolds stimulating macrophages polarization on osteogenesis was explored. The results showed that CaP Zn0.8Mn and CaP Zn0.8Mn0.1Li scaffolds could induce macrophages to polarize to M2, and the polarization trend was more obvious after adding Li element, which could effectively reduce the inflammatory response, and CaP Zn0.8Mn0.1Li scaffolds could stimulate macrophages to secrete more osteogenic factors, including BMP2 and VEGF, thus forming an immune microenvironment that was anti-inflammatory and beneficial to bone repair. It can effectively promote the osteogenic differentiation of MC3T3-E1. In vivo experiments also confirmed that after the addition of Mn/Li element, the inflammation was the weakest and the bone repair effect was the best. It was proved that CaP Zn-Mn-Li scaffolds were excellent bone replacement materials, which provided the basis for the development of bone replacement materials with targeted regulation of bone immune microenvironment.

Inspired by the excellent wear resistance and lubrication of articular joints, a novel bionic interfacial system was proposed by combining thixotropic hydrogel with surface porous Ultrahigh Molecular Weight Polyethylene (UHMWPE). Thixotropic hydrogel, synthesised by gelatin, alginate sodium, tannic acid and weak crosslinking by Ca2+ (Gel-TA-Alg@Ca2+), was used as a lubricant due to its shear-thinning when loaded, then the recovery viscosity to be benefitted for reserving in surface pores on UHMWPE when unloaded. Surface porous UHMWPE was fabricated by using hydroxyapatite particles as porogen to control its porosity, pore size, surface roughness and surface energy (PE-HA). Gel-TA-Alg@Ca2+ significantly reduced average coefficients of friction and wear factors compared to those under normal saline and calf serum solution lubricating after reciprocating tribological testing. Notably, Gel-TA-Alg@Ca2+ still maintained thixotropy and was stored in surface pores of UHMWPE even after tribological testing for 7200 min. Thus, durable lubrication could be realised due to the synergistic effect of surface porous structure and thixotropy. Stribeck curves showed the characterisations of mixed, elastohydrodynamic and hydrodynamic, but without boundary lubrications for PE-30HA under three lubricants. The present results might provide the potential application to construct the durable lubrication bionic articular joint interfacial system for artificial joints.

Bone regeneration of critical-sized bone defects, bone fractures or joint replacements remains a significant clinical challenge. Although there has been rapid advancement in both the fields of bone tissue engineering and additive manufacturing, functional bone implants with rapid vascularization capacity to ensure osseointegration and long-term biological fixation in large bone defects remains limited in clinics. In this study, we developed anin vitrovascularized bone implant by combining cell-laden hydrogels with direct metal printed (DMP) porous titanium alloys (Ti-6Al-4V). A 5 wt% allylated gelatin (GelAGE), was utilized to co-encapsulate human mesenchymal stromal cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) to investigate concurrent osteogenic and vasculogenic performance. DMP macro-porous Ti-6Al-4V scaffolds were subsequently infused/enriched with cell-laden GelAGE to examine the feasibility to deliver cells and engineer vascular-like networks in the hybrid implant. Furthermore, as a proof of concept, a full-scale porous Ti-6Al-4V acetabular cup was impregnated with cell-laden hydrogel to validate the clinical potential of this strategy. The vasculogenic potential was evaluated by examining micro-capillary formation coupled with capillary network maturation and stabilization. Osteogenic differentiation was assessed via alkaline phosphatase activity as well as osteocalcin and osteopontin expression. Our results suggested that GelAGE supported HUVECs spreading and vascular-like network formation, along with osteogenesis of hMSCs. Titanium hybrid constructs with cell-laden hydrogel demonstrated enhanced osteogenesis with similar vasculogenic capability compared to the cell-laden hydrogel alone constructs. The full-scale implant with cell-laden hydrogel coating similarly showed cell distribution and spreading, implying the potential for further clinical application. Our study presents the feasibility of integrating bio-functional hydrogels with porous titanium implants to fabricate a vascularized hybrid construct with both mechanical support and preferable biological functionality (osteogenesis/vasculogenesis), which paves the way for improved strategies to enhance bone regeneration in complex large bone defects achieving long-term bone-implant fixation.

Recently developed modular bioassembly techniques hold tremendous potential in tissue engineering and regenerative medicine, due to their ability to recreate the complex microarchitecture of native tissue. Here, we developed a novel approach to fabricate hybrid tissue-engineered constructs adopting high-throughput microfluidic and 3D bioassembly strategies. Osteochondral tissue fabrication was adopted as an example in this study, because of the challenges in fabricating load bearing osteochondral tissue constructs with phenotypically distinct zonal architecture. By developing cell-instructive chondrogenic and osteogenic bioink microsphere modules in high-throughput, together with precise manipulation of the 3D bioassembly process, we successfully fabricated hybrid engineered osteochondral tissue in vitro with integrated but distinct cartilage and bone layers. Furthermore, by encapsulating allogeneic umbilical cord blood-derived mesenchymal stromal cells, and demonstrating chondrogenic and osteogenic differentiation, the hybrid biofabrication of hydrogel microspheres in this 3D bioassembly model offers potential for an off-the-shelf, single-surgery strategy for osteochondral tissue repair.

Finding and constructing an osteogenic microenvironment similar to natural bone tissue has always been a frontier topic in orthopedics. We found that osteocytes are targeting cells controlling bone anabolism produced by PTH (JBMR 2017, PMID: 27704638), and osteocytes with activated Wnt signaling orchestrate bone formation and resorption (PNAS 2015, PMID: 25605937). However, methods for taking advantage of the leading role of osteocytes in bone regeneration remain unexplored. Herein, we found that the osteocytes with SKL2001-activated Wnt signaling could be an osteogenic microenvironment (SOOME) which upregulates the expression of bone transcription factor Runx2 and Bglap and promotes the differentiation of bone marrow stromal cell ST2 into osteoblasts. Interestingly, 60 μM SKL2001 treatment of osteocytic MLO-Y4 for 24 h maintained Wnt signaling activation for three days after removal, which was sufficient to induce osteoblast differentiation. Triptonide, a Wnt inhibitor, could eliminate this differentiation. Moreover, on day 5, the Wnt signaling naturally decreased to the level of the control group, indicating that this method of Wnt-signaling induction is safe to use. We quickly verified in vivo function of SOOME to a good proximation in 3D bioprinted modules composed of reciprocally printed polycaprolactone bundles (for support) and cell bundles (for bioactivity). In the cell bundles, SOOME stably supported the growth and development of ST2 cells, the 7-day survival rate was as high as 91.6%, and proliferation ability increased linearly. Similarly, SOOME greatly promoted ST2 differentiation and mineralization for 28 days. In addition, SOOME upregulated the expression of angiopoietin 1, promoted endothelial cell migration and angiogenesis, and increased node number and total length of tubes and branches. Finally, we found that the function of SOOME could be realized through the paracrine pathway. This study reveals that osteocytes with Wnt signaling activated by SKL2001 are a safe osteogenic microenvironment. Both SOOME itself and its cell-free culture supernatant can improve bioactivity for osteoblast differentiation, with composite scaffolds especially bearing application value.

Chemerin, a secreted protein mainly produced by adipocytes and hepatocytes, plays a variety of roles in endocrine or paracrine signaling. As reported in human epidemiology, chemerin was correlated with osteoporosis. And the previous in vitro study found that chemerin knockdown promoted osteogenesis and inhibited adipogenesis. However, the function of chemerin in bone metabolism and the underlying mechanism remains unclear. In this study, we uncovered the in vivo function of chemerin in bone homeostasis. We discovered that in obese mice, chemerin was increased in serum, while decreased in the bone marrow; and the chemerin expression in bone tissue was positively correlated with osteogenic genes. To further investigate the function of chemerin in bone metabolism, we generated chemerin deficiency and overexpression mice. We found bone mass and osteogenesis were decreased in chemerin deficiency mice, while were increased in chemerin overexpression mice. Furthermore, we observed that the chemerin expression increased during osteogenic differentiation of MSCs. Besides, we verified that chemerin promoted osteogenic differentiation in C3H10T1/2 cells and BMSCs through Akt/Gsk3β/β‐catenin axis. Treatment with Akt inhibitor (MK2206) abolished the promoting effect of chemerin on osteogenic differentiation and active β‐catenin. Together, our results suggest chemerin in bone marrow, not in serum, promotes osteogenic differentiation and bone formation via Akt/Gsk3β/β‐catenin axis. Chemerin may serve as a therapeutic strategy for osteoporosis.

There remains a critical need to develop new technologies and materials that can meet the demands of treating large bone defects. The advancement of 3-dimensional (3D) printing technologies has allowed the creation of personalized and customized bone grafts, with specific control in both macro- and micro-architecture, and desired mechanical properties. Nevertheless, the biomaterials used for the production of these bone grafts often possess poor biological properties. The incorporation of growth factors (GFs), which are the natural orchestrators of the physiological healing process, into 3D printed bone grafts, represents a promising strategy to achieve the bioactivity required to enhance bone regeneration. In this review, the possible strategies used to incorporate GFs to 3D printed constructs are presented with a specific focus on bone regeneration. In particular, the strengths and limitations of different methods, such as physical and chemical cross-linking, which are currently used to incorporate GFs to the engineered constructs are critically reviewed. Different strategies used to present one or more GFs to achieve simultaneous angiogenesis and vasculogenesis for enhanced bone regeneration are also covered in this review. In addition, the possibility of combining several manufacturing approaches to fabricate hybrid constructs, which better mimic the complexity of biological niches, is presented. Finally, the clinical relevance of these approaches and the future steps that should be taken are discussed.

Purpose Additive manufacturing (AM) has the potential to revolutionise the fabrication of complex surgical instruments. However, AM parts typically have a higher surface roughness compared to machined or fine cast parts. High surface roughness has important implications for surgical instruments, particularly in terms of cleanliness and aesthetic considerations. In this study, bulk surface finishing methods are described to produce end-use selective laser melting parts. Design/methodology/approach The aim was to achieve a surface finish as close as possible to machined parts (Ra = 0.9 µm, Wa = 0.2 µm, Pv = 7.3 µm). A sample coupon was designed to systematically evaluate different finishing techniques. Processes included bulk finishing, blasting and centrifugal finishing methods on individual parts, as well as heat treatment before and after surface finishing. Findings Abrasive blasting or centrifugal finishing alone was not adequate to achieve an end-use surface finish. White oxide vapour blasting at high water pressure was the most effective of the abrasive blasting processes. For centrifugal finishing, a 4 h runtime resulted in an acceptable reduction in surface roughness (Ra = 2.9 µm, Wa = 2.0 µm, Pv = 34.6 µm: inclined surface [30°]) while not significantly increasing part radii. The combination of finishing methods resulting in the smoothest surfaces was white oxide blasting followed by 4 h of centrifugal finishing and a final glass bead blast (Ra = 0.6 µm, Wa = 0.9 µm, Pv = 6.9 µm: inclined surface [30°]). The order of these methods was important because white oxide blasting was significantly less effective when applied after the centrifugal finishing. Originality/value Collectively, these results describe the development of a practical bulk finishing method for stainless steel surgical instruments produced by AM.

Adipocytes and immune cells are vital for the development of adipose tissue. Adipokines secreted by adipocytes regulate adipogenesis and body metabolism. Chemerin is one of the adipokines. However, the function and mechanism of chemerin in adipose tissue are not fully illuminated. Compared with wild type (WT) mice, Rarres2−/− mice gained weight and significantly increased fat distribution in subcutaneous adipose tissue (SAT), rather than visceral adipose tissue (VAT) on high fat diet (HFD). PPARγ and C/EBPα, the master regulators of adipogenesis, were up-regulated in SAT and down-regulated in VAT in Rarres2−/− mice comparing with WT mice. Inspite of chemerin deficiency or not, the ratio of adipocyte-progenitors to total cells and the differentiation capacity of adipocyte-progenitors were similar in SAT and VAT, but macrophage infiltration in VAT was more severe than in SAT in Rarres2−/− mice. Furthermore, CD45+ immune cells supernatant from Rarres2−/− SAT promoted the differentiation of adipocyte-progenitors and 3T3-L1 cells. Adipokine array assay of CD45+ immune cells supernatant revealed that metalloproteinase inhibitor 1 (TIMP1), an inhibitor of adipogenesis, was reduced in Rarres2−/− SAT, but increased in Rarres2−/− VAT. As we specifically knocked down chemerin in SAT, TIMP1 was down-regulated and adipogenesis was promoted with reducing infiltration of macrophages. The present study demonstrates that the effects of chemerin on adipose tissue is depot different, and specific knock down chemerin in SAT promote adipogenesis and improve glucose tolerance test (GTT) and insulin tolerance test (ITT). This suggests a potential therapeutic target for chemerin in the treatment of obesity related metabolic disorder.

In order to obtain bioactive bone-implant interfaces with enhanced osteogenic capacity, various approaches have been developed to modify surface physicochemical properties of bio-inert titanium and titanium alloys. One promising strategy involves fabricating highly ordered nanotubes (NT) on implant surfaces via electrochemical anodization. However, few studies have applied this technique to Ti-6Al-4V alloys most commonly adopted for the fabrication of osteo-integrated surfaces on orthopedic implants. In this study, we investigated the influence of electrolyte hydrodynamics to NT fabrication on Ti-6Al-4V in ethylene glycol based electrolyte and evaluated the osteogenic differentiation capacity of human mesenchymal stromal cells (hMSCs) on different diameter NT surfaces. Computational Fluid Dynamics (CFD) analysis was used to simulate electrolyte flow profiles under various stirring conditions (e.g. stirrer bar location and flow direction) and their correlation to NT formation. Polished Ti-6Al-4V disks (240 grit) were anodized at 20 and 40 V under optimal electrolyte flow conditions for comparison of NT diameter-controlled osteogenic differentiation and mineralization potential of hMSCs over 21 days culture in osteogenic media. Ti-6Al-4V surfaces anodized with 20 and 40 V resulted with NTs diameter approx. 39 and 83 nm, respectively. Electrolyte hydrodynamics (flow profile) significantly influenced the uniformity of NT formation. Here, a uniform velocity and shear stress profile at the surface promoted homogeneous NT growth, whereas large variation in either flow velocity or shear stress to the surface impaired mature NT formation. After 21 days of culture, fluorescence staining demonstrated significantly greater osteocalcin and osteopontin expression, and increased mineralized deposits (xylenol orange staining) on fluctuating NT surfaces anodized under 20 V (Ø 39 nm) relative to flat NT layer anodized with 40 V (Ø 83 nm) and polished controls. This study provides a systematic investigation of NT formation with respect to the electrolyte hydrodynamic effects to NT growth on Ti-6Al-4V alloys, demonstrating the feasibility of a one-step anodization process for generating uniform NT under optimal hydrodynamics. Optimized wavy micro-/nano-topography with Ø 39 nm NT stimulated osteogenic differentiation capacity of hMSCs on Ti-6Al-4V alloys and confirmed the potential application of anodization to improve osteo-integrative surfaces in orthopedic implants.

Additive manufacturing (AM) of titanium alloys offers the capacity to fabricate patient-specific implants with defined porous architecture to enhance bone-implant fixation. However, clinical challenges associated with orthopedic implants include inconsistent osseointegration and biofilm-associated peri-implant infection, leading to implant failure. Here, a strategy is developed to reduce infection and promote osteogenesis simultaneously on AM Ti-6Al-4V implants by delivering biofilm inhibitor molecules via titania nanotube surface modification. Electrochemical anodization is performed on polished and as-manufactured Ti-6Al-4V to generate nanotubes, which are utilized for delivery of a novel methylthioadenosine nucleosidase inhibitor (MTANi) that targets MTAN-a key enzyme in bacterial metabolism involved in biofilm formation-thereby offering biofilm inhibition capacity combined with surface nano-topography for promoting osteogenesis. Clinical isolates of staphylococcus cohnii formed firm biofilms on polished and AM Ti-6Al-4V controls whereas modified implants loaded with MTANi inhibit biofilm formation. Anodized AM Ti-6Al-4V nanotube substrates enhance alkaline phosphatase production, bone-specific protein expression (osteocalcin, collagen I) and mineral deposition of human mesenchymal stromal cells (hMSCs), compared to as-manufactured controls. Importantly, no detrimental effects on hMSC proliferation and osteogenic differentiation are observed for MTANi-loaded substrates. Application of novel MTANi and electrochemical anodization offers a promising strategy for titanium alloy implant surface modification.

3D bioprinting involves the combination of 3D printing technologies with cells, growth factors and biomaterials, and has been considered as one of the most advanced tools for tissue engineering and regenerative medicine (TERM). However, despite multiple breakthroughs, it is evident that numerous challenges need to be overcome before 3D bioprinting will eventually become a clinical solution for a variety of TERM applications. To produce a 3D structure that is biologically functional, cell-laden bioinks must be optimized to meet certain key characteristics including rheological properties, physico-mechanical properties, and biofunctionality; a difficult task for a single component bioink especially for extrusion based bioprinting. As such, more recent research has been centred on multicomponent bioinks consisting of a combination of two or more biomaterials to improve printability, shape fidelity and biofunctionality. In this article, multicomponent hydrogel-based bioink systems are systemically reviewed based on the inherent nature of the bioink (natural or synthetic hydrogels), including the most current examples demonstrating properties and advances in application of multicomponent bioinks, specifically for extrusion based 3D bioprinting. This review article will assist researchers in the field in identifying the most suitable bioink based on their requirements, as well as pinpointing current unmet challenges in the field.

Evolution of metallurgy and biomaterials has progressively shifted the focus of metallic bone-interfacing implant design from adequate mechanical strength and biocompatibility to rapid osseointegration and infection inhibition. The now relatively well-established technology - powder bed additive manufacturing (AM), offers the ability to fabricate porous implants with precise mechanical properties, topological pore architectures and patient-specific design functions, has revolutionized the production of customized multifunctional metallic implants for the individual patient with anatomic-specific requirement. Even though AM titanium and its alloy Ti-6Al-4V have been investigated and adopted for clinical application for decades, the development of porous AM titanium implants is far from complete and further research is required to achieve excellent long-term clinical performance. In this review, we summarize the current status of AM in bone-interfacing implant fabrication, with particular focus on the experimental outcomes of various factors that influence osseointegration, bone and vascular ingrowth as well as hybrid strategies to combat infection, including: pore size, porosity, pore structure, surface modification techniques and incorporation of biological factors. In addition, we also discuss the osteogenic capacity of constructs fabricated through different manufacturing methods and titanium alloys. To this end, we highlight the exciting prospect of AM for bone-interfacing implant manufacture through optimization via material development, implant design, bio-functionalization to clinical evaluation to provide enhanced patient specificity and long-term function.

鄂尔多斯盆地三叠系延长组原油和烃源岩的有机质组成、沉积环境和演化程度相近,以往采用正构烷烃、类异戊二烯烷烃、甾萜烷等生物标志化合物进行精细油源对比还存在着一定的困难.文中对鄂尔多斯盆地中部三叠系延长组长7～长9油层组三套烃源岩的生物标志化合物参数的系统精细研究,优选特征参数,对烃源岩的成熟度、沉积环境及母质来源进行分析.研究发现:C29甾烷ββ/(ββ+αα)、C29 Ts(C29藿烷+C29 Ts)、C?30/(C?30+C30藿烷)、姥植比和甾烷ααα20RC29/C27在表征研究区三套烃源岩成熟度及母质来源方面具有较好的效果.C29甾烷ββ/(ββ+αα)和C29 Ts(C29藿烷+C29 Ts)反映研究区不同层位成熟度差异不明显,但同层位不同地区存在差异,志丹县以东的靖边-安塞地区较低.C?30/(C?30+C30藿烷)、姥植比和ααα20RC29/C27甾烷显示不同层位烃源岩的沉积环境、母源输入有差异,长7和长8油层组烃源为弱还原-弱氧化条件下的半深湖-浅湖水生生物输入为主,长9油层组烃源岩以氧化-弱氧化条件下的湖沼高等植物输入为主.