Therapeutic potential of oncolytic viruses in the era of precision oncology

Oncolytic virus(OV)therapy has been shown to be an effective targeted cancer therapy treatment in recent years,providing an avenue of treatment that poses no damage to surrounding healthy tissues.Not only do OVs cause direct oncolysis,but they also amplify both innate and adaptive immune responses generating long-term anti-tumour immunity.Genetically engineered OVs have become the common promising strategy to enhance anti-tumour immunity,safety,and efficacy as well as targeted delivery.The studies of various OVs have been accomplished through phase I-III clinical trial studies.In addition,the uses of carrier platforms of organic materials such as polymer chains,liposomes,hydrogels,and cell carriers have played a vital role in the potentially targeted delivery of OVs.The mechanism,rational design,recent clinical trials,applications,and the development of targeted delivery platforms of OVs will be discussed in this review.

Fabrication,microstructure and properties of advanced ceramic-reinforced composites for dental implants:a review

The growing field of dental implant research and development has emerged to rectify the problems associated with human dental health issues. Bio-ceramics are widely used in the medical field, particularly in dental implants, ortho implants, and medical and surgical tools. Various materials have been used in those applications to overcome the limitations and problems associated with their performance and its impact on dental implants. In this article we review and describe the fabrication methods employed for ceramic composites, the microstructure analyses used to identify significant effects on fracture behaviour, and various methods of enhancing mechanical properties. Further, the collective data show that the sintering technique improves the density, hardness, fracture toughness, and flexural strength of alumina- and zirconia-based composites compared with other methods. Future research aspects and suggestions are discussed systematically.

Advances in electrode interface materials and modification technologies for brain-computer interfaces

Recent advances in neuroelectrode interface materials and modification technologies are reviewed. Brain-computer interface is the new method of human-computer interaction, which not only can realise the exchange of information between the human brain and external devices, but also provides a brand-new means for the diagnosis and treatment of brain-related diseases. The neural electrode interface part of brain-computer interface is an important area for electrical, optical and chemical signal transmission between brain tissue system and external electronic devices, which determines the performance of brain-computer interface. In order to solve the problems of insufficient flexibility, insufficient signal recognition ability and insufficient biocompatibility of traditional rigid electrodes, researchers have carried out extensive studies on the neuroelectrode interface in terms of materials and modification techniques. This paper introduces the biological reactions that occur in neuroelectrodes after implantation into brain tissue and the decisive role of the electrode interface for electrode function. Following this, the latest research progress on neuroelectrode materials and interface materials is reviewed from the aspects of neuroelectrode materials and modification technologies, firstly taking materials as a clue, and then focusing on the preparation process of neuroelectrode coatings and the design scheme of functionalised structures.

A comparative study of human and porcine-derived decellularised nerve matrices

Decellularised extracellular matrix(dECM)biomaterials originating from allogeneic and xenogeneic tissues have been broadly studied in the field of regenerative medicine and have already been used in clinical treatments.Allogeneic dECMs are considered more compatible,but they have the drawback of extremely limited human tissue sources.Their availability is also restricted by the health and age of the donors.To investigate the viability of xenogeneic tissues as a substitute for human tissues,we fabricated both porcine decellularised nerve matrix(pDNM)and human decellularised nerve matrix for a comprehensive comparison.Photomicrographs showed that both dECM scaffolds retained the ECM microstructures of native human nerve tissues.Proteomic analysis demonstrated that the protein compositions of both dECMs were also very similar to each other.Their functional ECM contents effectively promoted the proliferation,migration,and maturation of primary human Schwann cells in vitro.However,pDNM contained a few antigens that induced severe host immune responses in humanised mice.Interestingly,after removing theα-galactosidase antigen,the immune responses were highly alleviated and the pre-treated pDNM maintained a human decellularised nerve matrix-like pro-regenerative phenotype.Therefore,we believe that anα-galactosidase-free pDNM may serve as a viable substitute for human decellularised nerve matrix in future clinical applications.

Research progress and clinical translation of three-dimensional printed porous tantalum in orthopaedics

With continuous developments in additive manufacturing technology, tantalum (Ta) metal has been manufactured into orthopaedic implants with a variety of forms, properties and uses by three-dimensional printing. Based on extensive research in recent years, the design, processing and performance aspects of this new orthopaedic implant material have been greatly improved. Besides the bionic porous structure and mechanical characteristics that are similar to human bone tissue, porous tantalum is considered to be a viable bone repair material due to its outstanding corrosion resistance, biocompatibility, bone integration and bone conductivity. Numerous in vitro, in vivo, and clinical studies have been carried out in order to analyse the safety and efficacy of these implants in orthopaedic applications. This study reviews the most recent advances in manufacturing, characteristics and clinical application of porous tantalum materials.

Harvest of functional mesenchymal stem cells derived from in vivo osteo-organoids

Bone marrow-derived mesenchymal stem cells(BM-MSCs)play a crucial role in stem cell therapy and are extensively used in regenerative medicine research.However,current methods for harvesting BM-MSCs present challenges,including a low yield of primary cells,long time of in vitro expansion,and diminished differentiation capability after passaging.Meanwhile mesenchymal stem cells(MSCs)recovered from cell banks also face issues like toxic effects of cryopreservation media.In this study,we provide a detailed protocol for the isolation and evaluation of MSCs derived from in vivo osteo-organoids,presenting an alternative to autologous MSCs.We used recombinant human bone morphogenetic protein 2-loaded gelatin sponge scaffolds to construct in vivo osteo-organoids,which were stable sources of MSCs with large quantity,high purity,and strong stemness.Compared with protocols using bone marrow,our protocol can obtain large numbers of high-purity MSCs in a shorter time(6 days vs.12 days for obtaining passage 1 MSCs)while maintaining higher stemness.Notably,we found that the in vivo osteo-organoid-derived MSCs exhibited stronger anti-replicative senescence capacity during passage and amplification,compared to BM-MSCs.The use of osteo-organoid-derived MSCs addresses the conflict between the limitations of autologous cells and the risks associated with allogeneic sources in stem cell transplantation.Consequently,our protocol emerges as a superior alternative for both stem cell research and tissue engineering.

Organoid extracellular vesicle-based therapeutic strategies for bone therapy

With the rapid development of population ageing,bone-related diseases seriously affecting the life of the elderly.Over the past few years,organoids,cell clusters with specific functions and structures that are self-induced from stem cells after three-dimensional culture in vitro,have been widely used for bone therapy.Moreover,organoid extracellular vesicles(OEVs)have emerging as promising cell-free nanocarriers due to their vigoroso physiological effects,significant biological functions,stable loading capacity,and great biocompatibility.In this review,we first provide a comprehensive overview of biogenesis,internalisation,isolation,and characterisation of OEVs.We then comprehensively highlight the differences between OEVs and traditional EVs.Subsequently,we present the applications of natural OEVs in disease treatment.We also summarise the engineering modifications of OEVs,including engineering parental cells and engineering OEVs after isolation.Moreover,we provide an outlook on the potential of natural and engineered OEVs in bone-related diseases.Finally,we critically discuss the advantages and challenges of OEVs in the treatment of bone diseases.We believe that a comprehensive discussion of OEVs will provide more innovative and efficient solutions for complex bone diseases.

Systematic evaluation of three porcine-derived collagen membranes for guided bone regeneration

Guided bone regeneration is one of the most common surgical treatment modalities performed when an additional alveolar bone is required to stabilize dental implants in partially and fully edentulous patients.The addition of a barrier membrane prevents non-osteogenic tissue invasion into the bone cavity,which is key to the success of guided bone regeneration.Barrier membranes can be broadly classified as non-resorbable or resorbable.In contrast to non-resorbable membranes,resorbable barrier membranes do not require a second surgical procedure for membrane removal.Commercially available resorbable barrier membranes are either synthetically manufactured or derived from xenogeneic collagen.Although collagen barrier membranes have become increasingly popular amongst clinicians,largely due to their superior handling qualities compared to other commercially available barrier membranes,there have been no studies to date that have compared commercially available porcine-derived collagen membranes with respect to surface topography,collagen fibril structure,physical barrier property,and immunogenic composition.This study evaluated three commercially available non-crosslinked porcine-derived collagen membranes(Striate+TM,Bio-Gide®and CreosTM Xenoprotect).Scanning electron microscopy revealed similar collagen fibril distribution on both the rough and smooth sides of the membranes as well as the similar diameters of collagen fibrils.However,D-periodicity of the fibrillar collagen is significantly different among the membranes,with Striate+TM membrane having the closest D-periodicity to native collagen I.This suggests that there is less deformation of collagen during manufacturing process.All collagen membranes showed superior barrier property evidenced by blocking 0.2–16.4µm beads passing through the membranes.To examine the immunogenic agents in these membranes,we examined the membranes for the presence of DNA and alpha-gal by immunohistochemistry.No alpha-gal or DNA was detected in any membranes.However,using a more sensitive detection method(real-time polymerase chain reaction),a relatively strong DNA signal was detected in Bio-Gide®membrane,but not Striate+TM and CreosTM Xenoprotect membranes.Our study concluded that these membranes are similar but not identical,probably due to the different ages and sources of porcine tissues,as well as different manufacturing processes.We recommend further studies to understand the clinical implications of these findings.

Three-dimensional biofabrication of nanosecond laser micromachined nanofibre meshes for tissue engineered scaffolds

There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue.Three-dimensional(3D)printing offers a method of fabricating complex anatomical features of clinically relevant sizes.However,the construction of a scaffold to replicate the complex hierarchical structure of natural tissues remains challenging.This paper reports a novel biofabrication method that is capable of creating intricately designed structures of anatomically relevant dimensions.The beneficial properties of the electrospun fibre meshes can finally be realised in 3D rather than the current promising breakthroughs in two-dimensional(2D).The 3D model was created from commercially available computer-aided design software packages in order to slice the model down into many layers of slices,which were arrayed.These 2D slices with each layer of a defined pattern were laser cut,and then successfully assembled with varying thicknesses of 100μm or 200μm.It is demonstrated in this study that this new biofabrication technique can be used to reproduce very complex computer-aided design models into hierarchical constructs with micro and nano resolutions,where the clinically relevant sizes ranging from a simple cube of 20 mm dimension,to a more complex,50 mm-tall human ears were created.In-vitro cell-contact studies were also carried out to investigate the biocompatibility of this hierarchal structure.The cell viability on a micromachined electrospun polylactic-co-glycolic acid fibre mesh slice,where a range of hole diameters from 200μm to 500μm were laser cut in an array where cell confluence values of at least 85%were found at three weeks.Cells were also seeded onto a simpler stacked construct,albeit made with micromachined poly fibre mesh,where cells can be found to migrate through the stack better with collagen as bioadhesives.This new method for biofabricating hierarchical constructs can be further developed for tissue repair applications such as maxillofacial bone injury or nose/ear cartilage replacement in the future.

Global trends and hot topics in clinical applications of perovskite materials:a bibliometric analysis

In recent years,perovskite has received increasing attention in the medical field.However,there has been a lack of related bibliometric analysis in this research field.This study aims to analyse the research status and hot topics of perovskite in the medical field from a bibliometric perspective and explore the research direction of perovskite.This study collected 1852 records of perovskite research in the medical field from 1983 to 2022 in the Web of Science(WOS)database.The country,institution,journal,cited references,and keywords were analysed using CiteSpace,VOS viewer,and Bibliometrix software.The number of articles related to perovskite research in the medical field has been increasing every year.China and USA have published the most papers and are the main forces in this research field.The University of London Imperial College of Science,Technology,and Medicine is the most active institution and has contributed the most publications.ACS Applied Materials&Interfaces is the most prolific journal in this field.“Medical electronic devices”,“X-rays”,and“piezoelectric materials”are the most researched directions of perovskite in the medical field.“Performance”,“perovskite”,and“solar cells”are the most frequently used keywords in this field.Advanced Materials is the most relevant and academically influential journal for perovskite research.Halide perovskites have been a hot topic in this field in recent years and will be a future research trend.X-ray,electronic medical equipment,and medical stents are the main research directions.

Biological approaches to the repair and regeneration of the rotator cuff tendon-bone enthesis:a literature review

Entheses are highly specialised organs connecting ligaments and tendons to bones,facilitating force transmission,and providing mechanical strengths to absorb forces encountered.Two types of entheses,fibrocartilaginous and fibrous,exist in interfaces.The gradual fibrocartilaginous type is in rotator cuff tendons and is more frequently injured due to the poor healing capacity that leads to loss of the original structural and biomechanical properties and is attributed to the high prevalence of retears.Fluctuating methodologies and outcomes of biological approaches are challenges to overcome for them to be routinely used in clinics.Therefore,stratifying the existing literature according to different categories(chronicity,extent of tear,and studied population)would effectively guide repair approaches.This literature review supports tissue engineering approaches to promote rotator cuff enthesis healing employing cells,growth factors,and scaffolds period.Outcomes suggest its promising role in animal studies as well as some clinical trials and that combination therapies are more beneficial than individualized ones.It then highlights the importance of tailoring interventions according to the tear extent,chronicity,and the population being treated.Contributing factors such as loading,deficiencies,and lifestyle habits should also be taken into consideration.Optimum results can be achieved if biological,mechanical,and environmental factors are approached.It is challenging to determine whether variations are due to the interventions themselves,the animal models,loading regimen,materials,or tear mechanisms.Future research should focus on tailoring interventions for different categories to formulate protocols,which would best guide regenerative medicine decision making.

Mechanically conditioned cell sheets cultured on thermo-responsive surfaces promote bone regeneration

Cell sheet-based scaffold-free technology holds promise for tissue engineering applications and has been extensively explored during the past decades.However,efficient harvest and handling of cell sheets remain challenging,including insufficient extracellular matrix content and poor mechanical strength.Mechanical loading has been widely used to enhance extracellular matrix production in a variety of cell types.However,currently,there are no effective ways to apply mechanical loading to cell sheets.In this study,we prepared thermo-responsive elastomer substrates by grafting poly(N-isopropyl acrylamide)(PNIPAAm)to poly(dimethylsiloxane)(PDMS)surfaces.The effect of PNIPAAm grafting yields on cell behaviours was investigated to optimize surfaces suitable for cell sheet culturing and harvesting.Subsequently,MC3T3-E1 cells were cultured on the PDMS-g-PNIPAAm substrates under mechanical stimulation by cyclically stretching the substrates.Upon maturation,the cell sheets were harvested by lowering the temperature.We found that the extracellular matrix content and thickness of cell sheet were markedly elevated upon appropriate mechanical conditioning.Reverse transcription quantitative polymerase chain reaction and Western blot analyses further confirmed that the expression of osteogenic-specific genes and major matrix components were up-regulated.After implantation into the critical-sized calvarial defects of mice,the mechanically conditioned cell sheets significantly promoted new bone formation.Findings from this study reveal that thermo-responsive elastomer,together with mechanical conditioning,can potentially be applied to prepare high-quality cell sheets for bone tissue engineering.

Harnessing decellularised extracellular matrix microgels into modular bioinks for extrusion-based bioprinting with good printability and high post-printing cell viability

The printability of bioink and post-printing cell viability is crucial for extrusion-based bioprinting.A proper bioink not only provides mechanical support for structural fidelity,but also serves as suitable three-dimensional(3D)microenvironment for cell encapsulation and protection.In this study,a hydrogel-based composite bioink was developed consisting of gelatin methacryloyl(GelMA)as the continuous phase and decellularised extracellular matrix microgels(DMs)as the discrete phase.A flow-focusing microfluidic system was employed for the fabrication of cell-laden DMs in a high-throughput manner.After gentle mixing of the DMs and GelMA,both rheological characterisations and 3D printing tests showed that the resulting DM-GelMA hydrogel preserved the shear-thinning nature,mechanical properties,and good printability from GelMA.The integration of DMs not only provided an extracellular matrix-like microenvironment for cell encapsulation,but also considerable shear-resistance for high post-printing cell viability.The DM sizes and inner diameters of the 3D printer needles were correlated and optimised for nozzle-based extrusion.Furthermore,a proof-of-concept bioink composedg of RSC96 Schwann cells encapsulated DMs and human umbilical vein endothelial cell-laden GelMA was successfully bioprinted into 3D constructs,resulting in a modular co-culture system with distinct cells/materials distribution.Overall,the modular DM-GelMA bioink provides a springboard for future precision biofabrication and will serve in numerous biomedical applications such as tissue engineering and drug screening.

Bioactive elements manipulate bone regeneration

While bone tissue is known for its inherent regenerative abilities,various pathological conditions and trauma can disrupt its meticulously regulated processes of bone formation and resorption.Bone tissue engineering aims to replicate the extracellular matrix of bone tissue as well as the sophisticated biochemical mechanisms crucial for effective regeneration.Traditionally,the field has relied on external agents like growth factors and pharmaceuticals to modulate these processes.Although efficacious in certain scenarios,this strategy is compromised by limitations such as safety issues and the transient nature of the compound release and half-life.Conversely,bioactive elements such as zinc(Zn),magnesium(Mg)and silicon(Si),have garnered increasing interest for their therapeutic benefits,superior stability,and reduced biotic risks.Moreover,these elements are often incorporated into biomaterials that function as multifaceted bioactive components,facilitating bone regeneration via release on-demand.By elucidating the mechanistic roles and therapeutic efficacy of the bioactive elements,this review aims to establish bioactive elements as a robust and clinically viable strategy for advanced bone regeneration.

Bioactive peptides for anticancer therapies

Cancer is a serious concern in public health worldwide.Numerous modalities including surgery,radiotherapy,and chemotherapy,have been used for cancer therapies in clinic.Despite progress in anticancer therapies,the usage of these methods for cancer treatment is often related to deleterious side effects and multidrug resistance of conventional anticancer drugs,which have prompted the development of novel therapeutic methods.Anticancer peptides(ACPs),derived from naturally occurring and modified peptides,have received great attention in these years and emerge as novel therapeutic and diagnostic candidates for cancer therapies,because of several advantages over the current treatment modalities.In this review,the classification and properties of ACPs,the mode of action and mechanism of membrane disruption,as well as the natural sources of bioactive peptides with anticancer activities were summarised.Because of their high efficacy for inducing cancer cell death,certain ACPs have been developed to work as drugs and vaccines,evaluated in varied phases of clinical trials.We expect that this summary could facilitate the understanding and design of ACPs with increased specificity and toxicity towards malignant cells and with reduced side effects to normal cells.

Animal models for testing biomaterials in periodontal regeneration

Periodontitis is a prevalent oral disease. It can cause tooth loss and has a significant impact on patients’ quality of life. While existing treatments can only slow the progression of periodontitis, they are unable to achieve complete regeneration and functional reconstruction of periodontal tissues. As a result, regenerative therapies based on biomaterials have become a focal point of research in the field of periodontology. Despite numerous studies reporting the superiority of new materials in periodontal regeneration, limited progress has been made in translating these findings into clinical practice. This may be due to the lack of appropriate animal models to simulate the tissue defects caused by human periodontitis. This review aims to provide an overview of established animal models for periodontal regeneration, examine their advantages and limitations, and outline the steps for model construction. The objective is to determine the most relevant animal models for periodontal regeneration based on the hypothesis and expected outcomes.

Mechanical environment for in vitro cartilage tissue engineering assisted by in silico models

Mechanobiological study of chondrogenic cells and multipotent stem cells for articular cartilage tissue engineering(CTE)has been widely explored.The mechanical stimulation in terms of wall shear stress,hydrostatic pressure and mechanical strain has been applied in CTE in vitro.It has been found that the mechanical stimulation at a certain range can accelerate the chondrogenesis and articular cartilage tissue regeneration.This review explicitly focuses on the study of the influence of the mechanical environment on proliferation and extracellular matrix production of chondrocytes in vitro for CTE.The multidisciplinary approaches used in previous studies and the need for in silico methods to be used in parallel with in vitro methods are also discussed.The information from this review is expected to direct facial CTE research,in which mechanobiology has not been widely explored yet.

Recent advances of medical polyhydroxyalkanoates in musculoskeletal system

Infection and rejection in musculoskeletal trauma often pose challenges for natural healing,prompting the exploration of biomimetic organ and tissue transplantation as a common alternative solution.Polyhydroxyalkanoates(PHAs)are a large family of biopolyesters synthesised in microorganism,demonstrating excellent biocompatibility and controllable biodegradability for tissue remodelling and drug delivery.With different monomer-combination and polymer-types,multi-mechanical properties of PHAs making them have great application prospects in medical devices with stretching,compression,twist in long time,especially in musculoskeletal tissue engineering.This review systematically summarises the applications of PHAs in multiple tissues repair and drug release,encompassing areas such as bone,cartilage,joint,skin,tendons,ligament,cardiovascular tissue,and nervous tissue.It also discusses challenges encountered in their application,including high production costs,potential cytotoxicity,and uncontrollable particle size distribution.In conclusion,PHAs offer a compelling avenue for musculoskeletal system applications,striking a balance between biocompatibility and mechanical performance.However,addressing challenges in their production and application requires further research to unleash their full potential in tackling the complexities of musculoskeletal regeneration.

Fabrication of magnesium-doped porous polylactic acid microsphere for bone regeneration

Biodegradable polymer microspheres that can be used as drug carriers are of great importance in biomedical applications,however,there are still challenges in controllable preparation of microsphere surface morphology and improvement of bioactivity.In this paper,firstly,poly(L-lactic acid)(PLLA)was synthesised by ring-opening polymerisation under anhydrous anaerobic conditions and further combined with the emulsion method,biodegradable PLLA microspheres(PM)with sizes ranging from 60-100μm and with good sphericity were prepared.In addition,to further improve the surface morphology of PLLA microspheres and enhance their bioactivity,functionalised porous PLLA microspheres loaded with magnesium oxide(MgO)/magnesium carbonate(MgCO_(3))(PMg)were also prepared by the emulsion method.The results showed that the loading of MgO/MgCO_(3)resulted in the formation of a porous structure on the surface of the microspheres(PMg)and the dissolved Mg^(2+)could be released slowly during the degradation of microspheres.In vitro cellular experiments demonstrated the good biocompatibility of PM and PMg,while the released Mg^(2+)further enhanced the anti-inflammatory effect and osteogenic activity of PMg.Functionalised PMg not only show promise for controlled preparation of drug carriers,but also have translational potential for bone regeneration.

The emergence of AI tools in scientific writing and research

Biomaterials Translational is now in its third year since its establishment.On March 19,the first virtual forums in 2023 on‘Advanced Technology for Biomaterial Research’hosted by Biomaterials Translational received a great response.The forum covered topics including angiogenesis of biomaterials presented by Professor Jake Barralet,McGill University,Canada,and a new lasermicrotome technology from Dr.Heiko Rechter,LLS ROWIAK LaserLabSolutions,Germany.Lasermicrotome and its related platform are expected to have wide applications for histology,pathology,and tissue/biomaterial interfaces,as shown in the cover art.