An injectable curcumin-releasing organohydrogel with non-drying property and high mechanical stability at low-temperature for expe dite d skin wound care

Although hydrogels have demonstrated great potential as new wound dressing materials,their instability in shape and/or mechanical characteristics due to water loss or freezing remains a shortcoming for wound care application.Herein,a novel injectable organohydrogel(IOH)of physically crosslinked polyvinyl alco-hol/glycerol that possesses non-drying capability and high stability at low temperature was developed for wound care.IOH has a skin-like stiffness(G’,∼280 Pa),high injectability,self-healing capability,high water-vapor transmission rate,and bacterial inhibitory effect.IOH exhibits high shape and mechanical stabilities after curing at 37°C and 50%relative humidity for 7 days or after curing at-20°C for 1 day.In addition,glycerol in IOH enabled an efficient loading and release of water-insoluble curcumin,a well-known anti-bacterial and anti-inflammation drug.The curcumin-releasing IOH(Cur-IOH)demonstrated significantly enhanced anti-bacterial performance compared to IOH or curcumin-loading polyvinyl alco-hol hydrogel.More importantly,Cur-IOH could accelerate wound healing in a murine full-thickness skin defect wound model,revealing improved wound contraction,collagen deposition,angiogenesis,and epi-dermis formation.This study demonstrates the great potential of organohydrogel for the reparation of severe wounds and Cur-IOH as a new type of injectable wound healing material.

Mussel-inspired multifunctional coating for bacterial infection prevention and osteogenic induction

Bacterial infection and osteogenic integration are the two main problems that cause severe complications after surgeries. In this study, the antibacterial and osteogenic properties were simultaneously introduced in biomaterials, where copper nanoparticles(Cu NPs) were generated by in situ reductions of Cu ions into a mussel-inspired hyperbranched polyglycerol(MI-h PG) coating via a simple dip-coating method.This hyperbranched polyglycerol with 10 % catechol groups’ modification presents excellent antifouling property, which could effectively reduce bacteria adhesion on the surface. In this work, polycaprolactone(PCL) electrospun fiber membrane was selected as the substrate, which is commonly used in biomedical implants in bone regeneration and cardiovascular stents because of its good biocompatibility and easy post-modification. The as-fabricated Cu NPs-incorporated PCL membrane [PCL-(MI-h PG)-Cu NPs]was confirmed with effective antibacterial performance via in vitro antibacterial tests against Staphylococcus aureus(S. aureus), Escherichia coli(E. coli), and multi-resistant E. coli. In addition, the in vitro results demonstrated that osteogenic property of PCL-(MI-h PG)-Cu NPs was realized by upregulating the osteoblast-related gene expressions and protein activity. This study shows that antibacterial and osteogenic properties can be balanced in a surface coating by introducing Cu NPs.

3D bioprinting of cell-laden nano-attapulgite/gelatin methacrylate composite hydrogel scaffolds for bone tissue repair

Bone tissue engineering(BTE)has proven to be a promising strategy for bone defect repair.Due to its excellent biological properties,gelatin methacrylate(GelMA)hydrogels have been used as bioinks for 3D bioprinting in some BTE studies to produce scaffolds for bone regeneration.However,applications for load-bearing defects are limited by poor mechanical properties and a lack of bioactivity.In this study,3D printing technology was used to create nano-attapulgite(nano-ATP)/GelMA composite hydrogels loaded into mouse bone mesenchymal stem cells(BMSCs)and mouse umbilical vein endothelial cells(MUVECs).The bioprintability,physicochemical properties,and mechanical properties were all thoroughly evaluated.Our findings showed that nano-ATP groups outperform the control group in terms of printability,indicating that nano-ATP is beneficial for printability.Additionally,after incorporation with nano-ATP,the mechanical strength of the composite hydrogels was significantly improved,resulting in adequate mechanical properties for bone regeneration.The presence of nano-ATP in the scaffolds has also been stud-ied for cell-material interactions.The findings show that cells within the scaffold not only have high viability but also a clear proclivity to promote osteogenic differentiation of BMSCs.Besides,the MUVECs-loaded composite hydrogels demonstrated increased angiogenic activity.A cranial defect model was also developed to evaluate the bone repair capability of scaffolds loaded with rat BMSCs.According to histo-logical analysis,cell-laden nano-ATP composite hydrogels can effectively im prove bone regeneration and promote angiogenesis.This study demonstrated the potential of nano-ATP for bone tissue engineering,which should also increase the clinical practicality of nano-ATP.

Mechano-active biomaterials for tissue repair and regeneration

There is a lack of effective tissue repair and regeneration strategies in current clinical practices.Numerous studies have suggested that smart or responsive biomaterials possessing the ability to respond to endogenous stimuli in vivo may positively mediate the tissue micro-environment towards a tissue repair or regeneration.Mechanical stimuli,which constantly exist in a wide range of biological systems and are involved in almost all the physiological processes,belong to such stimuli to which responsive biomaterials can respond.In recent studies,a new type of smart biomaterials,which can dynamically adapt to the mechanical stimuli in vivo and thus has specific functionality consistently mediated by such mechanical stimuli,has emerged.In contrast to common biomaterials that passively react to the mechanical environment of an implantation site,such mechano-active biomaterials have enabled various active or automatic strategies for tissue repair or regeneration,such as providing precise spatial-temporal controls on delivery of drugs or cells in the organs of the musculoskeletal and the circulatory systems;in situ reconstructing the original or a favorable mechanical environment at a lesion site;and accelerating the tissue remodeling or healing process via a mechanobiological effect.This article elucidates a perspective of perfecting tissue repair or regeneration using mechano-active biomaterials,especially highlighting the rationale behind the concept of mechano-active biomaterials and their potential in the repair or regeneration of musculoskeletal and cardiovascular tissues.Albeit outstanding challenges and unknowns,the emergence of mechano-active biomaterials has become a new avenue for tissue engineering and regenerative medicine.

Macroporous and Antibacterial Hydrogels Enabled by Incorporation of Mg-Cu Alloy Particles for Accelerating Skin Wound Healing

Repair of severe skin tissue injury remains a great challenge and wound infection is still a formidable problem.In this study,new macroporous and antibacterial gelatin/alginate(SAG)-based hydrogels for wound repair were designed and developed based on in-situ gas foaming method and ion release strategy as a result of Mg-Cu particles degradation in the hydrogel matrix.The addition of Mg-Cu particles decreased the storage modulus of SAG,maintained its mechanical resilience and enhanced its water-absorbing capability.Moreover,the water vapor transmission rate of SAG added with 2 wt.%Mg-Cu(SAG-2 MC)was 124%of that of medical gauze and 804%of commercial Tegaderm^(TM)film dressing.The bacterial inhibition rates of SAG-2 MC against S.aureus.E.coli and P.aeruginosa reached 99.9%±0.1%,98.7%±1.2%and 98.0%±0.7%,respectively,significantly greater than those of the SAG hydrogel and Mg particle-modified hydrogels.In addition,SAG-2 MC hydrogel was biocompatible and promoted cell migration.In vivo experiment results indicated that SAG-2 MC significantly accelerated the skin wound healing in murine model as demonstrated by higher epidermis thickness,more collagen deposition and enhanced angiogenesis compared with SAG-OMC,SAG-2 M and TegadermTM film.In summary,Mg-Cu particles have great potential to modulate the physiochemical and biological properties of SAG hydrogels.Mg-Cu particle-modified SAG hydrogels reveal significant promise in the treatment of severe skin wound or other soft tissue lesions.

Biomaterials and regulatory science

The fast development of both biomaterials and regulatory science calls for a convergence,which is addressed in this article via their link through medical products of biomaterials and related safety and efficacy evaluation.The updated definition of biomaterials,and concepts of biomaterials-related medical products and so-called medical-grade and implantable materials are firstly introduced.Then a brief overview of the concept and history of regulatory science and its assessment of safety and efficacy of medical products,as well as the currently ongoing biomaterials-related regulatory science programs are presented.Finally,the opportunities provided by regulatory science for biomaterials as well as challenges on how to develop a biomaterials-based regulatory science system are discussed.As the first article in the field to elucidate the relationship between biomaterials and regulatory science,key take-home messages include(1)biomaterials alone are not medical products;(2)regulatory authorities approve/clear final medical products,not biomaterials;(3)there is no definition/regulation on the so-called medical-grade or implantable materials;and(4)safety and efficacy refer to final medical products,not biomaterials alone.

Function-oriented design:A novel strategy for advanced biomedical materials

It has always been a dream to construct tissues and even organs for transplantation to replace those with defects caused by diseases or injuries.Tissue engineering is another milestone in the developmental history of life science after cellular and molecular bioscience.Nevertheless,despite decades of rapid de-velopment,tissue-engineered biomaterials have not been widely used clinically.Biomaterials constructed by physical and chemical methods have lots of difficulty in precisely mimicking the macroscopic and mi-croscopic structures of human tissues.The ultimate way to build organoid tissue for regeneration is to enable the cells to take the initiative and build suitable functions.Based on the thoughts of tissue engi-neering,organoid technology holds great potential as a research tool for a wide range of fields,including developmental biology,disease pathology,cell biology,precision medicine,and drug toxicity and efficacy testing.This technology also holds tremendous potential for regenerative medicine,as organoids present the possibility for autologous and allogeneic cell therapy through the replacement of damaged or dis-eased tissues with organoid-propagated tissue or stem cell populations.In this review work,we briefly outlook the development history of organoid technology,summarize the current bottlenecks and the un-derlying reasons,and propose the unified term“function-oriented design in tissue engineering”,a new topic that may provide a solution to overcome these bottlenecks.

Antibacterial behavior and related mechanisms of martensitic Cu-bearing stainless steel evaluated by a mixed infection model of Escherichia coli and Staphylococcus aureus in vitro

Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)are the most typical pathogenic bacteria with a significantly high risk of bio-contamination,widely existing in hospital and public places.Recent studies on antibacterial materials and the related mechanisms have attracted more interests of researchers.However,the antibacterial behavior of materials is usually evaluated separately on the single bacterial strain,which is far from the practical condition.Actually,the interaction between the polymicrobial communities can promote the growing profile of bacteria,which may weaken the antibacterial effect of materials.In this work,a 420 copper-bearing martensitic stainless steel(420 CuSS)was studied with respect to its antibacterial activity and the underlying mechanism in a co-culturing infection model using both E.coli and S.au reus.Observed via plating and counting colony forming units(CFU),Cu releasing,and material characterization,420 CuSS was proved to present excellent antibacterial performance against the mixed bacteria with an approximately 99.4%of antibacterial rate.In addition,420 CuSS could effectively inhibit the biofilm formation on its surfaces,resulting from a synergistic antibacterial effect of Cu ions,Fe ions,reactive oxygen species(ROS),and proton consumption of bacteria.

Starch-based adhesive hydrogel with gel-point viscoelastic behavior and its application in wound sealing and hemostasis

Hydrogels with tissue adhesiveness have demonstrated great promise for wearable electronics,artificial skin,soft robotics,and tissue repair.Nevertheless,adhesive hydrogels that are capable of sealing and hemostasis of wound with severe hemorrhage still lack.For this purpose,a series of ionically crosslinked starch hydrogels were developed here.The viscoelastic properties and tissue adhesiveness of the starch hydrogels were investigated.It is shown that the starch and cross linkers had significant influence on the viscoelastic properties of the starch hydrogels,which further resulted in varied tissue adhesiveness.Among the starch gels,there was one exhibiting a unique and stable"Gel Point"viscoelastic characteristic and it was named as gel-point adhesive hydrogel(GPAH).GPAH showed electrical conductivity,high tissue adhesiveness,high stretch-ability,self-healing capability,injectability,and degradability.The GPAH also exhibited high cytocompatibility,low hemolysis risk,and strong antibacterial effect.The wound sealing and hemostatic performance of GPAH was further evaluated by a rat femoral artery injury model.The blood loss after the sealing of GPAH(2.4±1.3 g)was significantly decreased compared to the group using gauze for sealing(6.3±1.5 g).Meanwhile,GPAH did not cause pathological changes of the soft tissues surrounding the wound.The above results indicate that GPAH,with high tissue adhesiveness,suitable viscoelastic property,strong antibacterial capacity,as well as electro-conductivity,bears great potential for the applications in smart wound management.

Characteristics of novel Ti-10Mo-xCu alloy by powder metallurgy for potential biomedical implant applications

When biomaterials are implanted in the human body,the surfaces of the implants become favorable sites for microbial adhesion and biofilm formation,causing peri-implant infection which frequently results in the failure of prosthetics and revision surgery.Ti-Mo alloy is one of the commonly used implant materials for load-bearing bone replacement,and the prevention of infection of Ti-Mo implants is therefore crucial.In this study,bacterial inhibitory copper(Cu)was added to Ti-Mo matrix to develop a novel Ti-Mo-Cu alloy with bacterial inhibitory property.The effects of Cu content on microstructure,tensile properties,cytocompatibility,and bacterial inhibitory ability of Ti-Mo-Cu alloy were systematically investigated.Results revealed that Ti-10Mo-1Cu alloy consisted ofαandβphases,while there were a few Ti2Cu intermetallic compounds existed for Ti-10Mo-3Cu and Ti-10Mo-5Cu alloys,in addition toαandβphases.The tensile strength of Ti-10Mo-xCu alloy increased with Cu content while elongation decreased.Ti-10Mo-3Cu alloy exhibited an optimal tensile strength of 1098.1 MPa and elongation of 5.2%.Cytocompatibility study indicated that none of the Ti-10Mo-xCu alloys had a negative effect on MC3T3-E1 cell proliferation.Bacterial inhibitory rates against S.aureus and E.coli increased with the increase in Cu content of Ti-10Mo-xCu alloy,within the ranges of 20-60%and 15-50%,respectively.Taken together,this study suggests that Ti-10Mo-3Cu alloy with high strength,acceptable elongation,excellent cytocompatibility,and the bacterial inhibitory property is a promising candidate for biomedical implant applications.

Injectable hydrogel wound dressing based on strontium ion cross-linked starch

Severe skin wounds cause great problems and sufferings to patients.In this study,an injectable wound dressing based on strontium ion cross-linked starch hydrogel(SSH)was developed and evaluated.The good inject-ability of SSH made it easy to be delivered onto the wound surface.The good tissue adhesiveness of SSH ensured a firm protection of the wound.Besides,SSH supported the proliferation of NIH/3T3 fibroblasts and facilitated the migration of human umbilical vein endothelial cells(HUVECs).Importantly,SSH exhibited strong antibacterial effects on Staphylococcus aiireiis(S.ai/rec/s),which could prevent wound infection.These results demonstrate that SSH is a promising wound dressing material for promoting wound healing.