Refractory metal niobium(Nb) incorporated with a small amount of silver(Ag),the resulting Nb-Ag twophase alloys,were fabricated by mechanical alloying and spark plasma sintering.The microstructure,mechanical propertie...Refractory metal niobium(Nb) incorporated with a small amount of silver(Ag),the resulting Nb-Ag twophase alloys,were fabricated by mechanical alloying and spark plasma sintering.The microstructure,mechanical properties,wear resistance,corrosion behavior,in vitro and in vivo antibacterial properties and biocompatibility of the Nb-Ag alloys were systematically investigated.The results show that the mechanical properties,wear resistance,corrosion resistance and antibacterial ability were significantly enhanced after addition of 5 at.% Ag.The fabricated Nb-5 at.% Ag alloy demonstrates high yield strength of up to ~1486 MPa and fracture strain of ~35 %.The precipitated Ag particles could reduce friction and wear.The enhanced corrosion resistance was attributed to the higher relative density of the sintered alloys and the formation of a stable and dense passive film of niobium and silver oxides.In vitro and in vivo evaluations show that the Nb-5 at.% Ag alloy also has strong antibacterial activity and good biocompatibility and osteointegration ability.These results demonstrate great potential of the nanostructured Nb-Ag alloys for dental and orthopedic implants.展开更多
Objective and Impact Statement.Real-time monitoring of the temperatures of regional tissue microenvironments can serve as the diagnostic basis for treating various health conditions and diseases.Introduction.Tradition...Objective and Impact Statement.Real-time monitoring of the temperatures of regional tissue microenvironments can serve as the diagnostic basis for treating various health conditions and diseases.Introduction.Traditional thermal sensors allow measurements at surfaces or at near-surface regions of the skin or of certain body cavities.Evaluations at depth require implanted devices connected to external readout electronics via physical interfaces that lead to risks for infection and movement constraints for the patient.Also,surgical extraction procedures after a period of need can introduce additional risks and costs.Methods.Here,we report a wireless,bioresorbable class of temperature sensor that exploits multilayer photonic cavities,for continuous optical measurements of regional,deep-tissue microenvironments over a timeframe of interest followed by complete clearance via natural body processes.Results.The designs decouple the influence of detection angle from temperature on the reflection spectra,to enable high accuracy in sensing,as supported by in vitro experiments and optical simulations.Studies with devices implanted into subcutaneous tissues of both awake,freely moving and asleep animal models illustrate the applicability of this technology for in vivo measurements.Conclusion.The results demonstrate the use of bioresorbable materials in advanced photonic structures with unique capabilities in tracking of thermal signatures of tissue microenvironments,with potential relevance to human healthcare.展开更多
Bone tissue regeneration holds the potential to solve both osteoporosis and large skeletal defects,two problems associated with significant morbidity.The differentiation of mesenchymal stem cells into the osteogenic l...Bone tissue regeneration holds the potential to solve both osteoporosis and large skeletal defects,two problems associated with significant morbidity.The differentiation of mesenchymal stem cells into the osteogenic lineage requires a specific microenvironment and certain osteogenic growth factors.Neural EGF Like-Like molecule 1(NELL-1)is a secreted glycoprotein that has proven,both in vitro and in vivo,to be a potent osteo-inductive factor.Furthermore,it has been shown to repress adipogenic differentiation and inflammation.NELL-1 can work synergistically with other osteogenic factors such as Bone Morphogenic Protein(BMP)2 and9,and has shown promise for use in tissue engineering and as a systemically administered drug for the treatment of osteoporosis.Here we provide a comprehensive up-to-date review on the molecular signaling cascade of NELL-1 in mesenchymal stem cells and potential applications in bone regenerative engineering.展开更多
Implant-associated infections are generally difficult to cure owing to the bacterial antibiotic resistance which is attributed to the widespread usage of antibiotics.Given the global threat and increasing influence of...Implant-associated infections are generally difficult to cure owing to the bacterial antibiotic resistance which is attributed to the widespread usage of antibiotics.Given the global threat and increasing influence of antibiotic resistance,there is an urgent demand to explore novel antibacterial strategies other than using antibiotics.Recently,using a certain surface topography to provide a more persistent antibacterial solution attracts more and more attention.However,the clinical application of biomimetic nano-pillar array is not satisfactory,mainly because its antibacterial ability against Gram-positive strain is not good enough.Thus,the pillar array should be equipped with other antibacterial agents to fulfill the bacteriostatic and bactericidal requirements of clinical application.Here,we designed a novel model substrate which was a combination of periodic micro/nano-pillar array and TiO2 for basically understanding the topographical bacteriostatic effects of periodic micro/nano-pillar array and the photocatalytic bactericidal activity of TiO2.Such innovation may potentially exert the synergistic effects by integrating the persistent topographical antibacterial activity and the non-invasive X-ray induced photocatalytic antibacterial property of TiO2 to combat against antibiotic-resistant implant-associated infections.First,to separately verify the topographical antibacterial activity of TiO2 periodic micro/nano-pillar array,we systematically investigated its effects on bacterial adhesion,growth,proliferation,and viability in the dark without involving the photocatalysis of TiO2.The pillar array with sub-micron motif size can significantly inhibit the adhesion,growth,and proliferation of Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli).Such antibacterial ability is mainly attributed to a spatial confinement size-effect and limited contact area availability generated by the special topography of pillar array.Moreover,the pillar array is not lethal to S.aureus and E.coli in 24 h.Then,the X-ray induced photocatalytic antibacterial property of TiO2 periodic micro/nano-pillar array in vitro and in vivo will be systematically studied in a future work.This study could shed light on the direction of surface topography design for future medical implants to combat against antibiotic-resistant implant-associated infections without using antibiotics.展开更多
With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical...With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical treatments.This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient.The most promising potential treatment options rely on stem cellbased therapies.Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function.Clinical approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing capacity.We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential.Given the current problems and complications presented by chronic wounds,we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care.展开更多
Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.A...Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration.展开更多
Approaches to regenerating bone often rely on integrating biomaterials and biological signals in the form of cells or cytokines.However,from a translational point of view,these approaches are challenging due to the so...Approaches to regenerating bone often rely on integrating biomaterials and biological signals in the form of cells or cytokines.However,from a translational point of view,these approaches are challenging due to the sourcing and quality of the biologic,unpredictable immune responses,complex regulatory paths,and high costs.We describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system(CSS)that offers distinct advantages for clinical translation.The CSS comprises a 3D-printed porous polydiolcitrate-hydroxyapatite composite elastomer infused with a polydiolcitrate-graphene oxide hydrogel composite.Using a micro-continuous liquid interface production 3D printer,we fabricate a precise porous ceramic scaffold with 60 wt%hydroxyapatite resembling natural bone.The resulting scaffold integrates with a thermoresponsive hydrogel composite in situ to fit the defect,which is expected to enhance surface contact with surrounding tissue and facilitate biointegration.The antioxidative properties of citrate polymers prevent long-term inflammatory responses.The CSS stimulates osteogenesis in vitro and in vivo.Within 4 weeks in a calvarial critical-sized bone defect model,the CSS accelerated ECM deposition(8-fold)and mineralized osteoid(69-fold)compared to the untreated.Through spatial transcriptomics,we demonstrated the comprehensive biological processes of CSS for prompt osseointegration.Our material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages,potentially expediting clinical application for bone reconstruction surgeries.展开更多
Chronic bladder dysfunction due to bladder disease or trauma is detrimental to affected patients as it can lead to increased risk of upper urinary tract dysfunction. Current treatment options include surgical interven...Chronic bladder dysfunction due to bladder disease or trauma is detrimental to affected patients as it can lead to increased risk of upper urinary tract dysfunction. Current treatment options include surgical interventions that enlarge the bladder with autologous bowel tissue to alleviate pressure on the upper urinary tract. This highly invasive procedure, termed bladder augmentation enterocystoplasty (BAE), significantly increases the risk of patient morbidity and mortality due to the incompatibility between bowel and bladder tissue. Therefore, patients would significantly benefit from an alternative treatment strategy that can regenerate healthy tissue and restore overall bladder function. Previous research has demonstrated the potential of citrate-based scaffolds co-seeded with bone marrow-derived stem/progenitor cells as an alternative graft for bladder augmentation. Recognizing that contact guidance can potentially influence tissue regeneration, we hypothesized that microtopographically patterned scaffolds would modulate cell responses and improve overall quality of the regenerated bladder tissue. We fabricated microgrooved (MG) scaffolds using the citrate-based biomaterial poly (1,8-octamethylene-citrate-co-octanol) (POCO) and co-seeded them with human bone marrow-derived mesenchymal stromal cells (MSCs) and CD34+ hematopoietic stem/progenitor cells (HSPCs). MG POCO scaffolds supported MSC and HSPC attachment, and MSC alignment within the microgrooves. All scaffolds were characterized and assessed for bladder tissue regeneration in an established nude rat bladder augmentation model. In all cases, normal physiological function was maintained post-augmentation, even without the presence of stem/progenitor cells. Urodynamic testing at 4-weeks post-augmentation for all experimental groups demonstrated that bladder capacity increased and bladder compliance was normal. Histological evaluation of the regenerated tissue revealed that cell-seeded scaffolds restored normal bladder smooth muscle content and resulted in increased revascularization and peripheral nerve regeneration. The presence of microgrooves on the cell-seeded scaffolds increased microvasculature formation by 20 % and urothelial layer thickness by 25 % in the regenerating tissue. Thus, this work demonstrates that microtopography engineering can influence bladder tissue regeneration to improve overall anatomical structure and re-establish bladder physiology.展开更多
基金financially supported by the Natural Science Foundation of Guangdong(Grant No.2019A1515011755)the Fundamental Research Program of Shenzhen(Grant Nos.JCYJ20170412153039309 and JCYJ20170307110418960)the Natural Science Foundation of Tianjin(General Program,No.18JCYBJC19500),China。
文摘Refractory metal niobium(Nb) incorporated with a small amount of silver(Ag),the resulting Nb-Ag twophase alloys,were fabricated by mechanical alloying and spark plasma sintering.The microstructure,mechanical properties,wear resistance,corrosion behavior,in vitro and in vivo antibacterial properties and biocompatibility of the Nb-Ag alloys were systematically investigated.The results show that the mechanical properties,wear resistance,corrosion resistance and antibacterial ability were significantly enhanced after addition of 5 at.% Ag.The fabricated Nb-5 at.% Ag alloy demonstrates high yield strength of up to ~1486 MPa and fracture strain of ~35 %.The precipitated Ag particles could reduce friction and wear.The enhanced corrosion resistance was attributed to the higher relative density of the sintered alloys and the formation of a stable and dense passive film of niobium and silver oxides.In vitro and in vivo evaluations show that the Nb-5 at.% Ag alloy also has strong antibacterial activity and good biocompatibility and osteointegration ability.These results demonstrate great potential of the nanostructured Nb-Ag alloys for dental and orthopedic implants.
基金This work utilized Northwestern University Micro/Nano Fabrication Facility(NUFAB)which is partially supported by Soft and Hybrid Nanotechnology Experimental(SHyNE)Resource(NSF ECCS-1542205)+3 种基金the Materials Research Science and Engineering Center(DMR-1720139)the State of Illinois,and Northwestern University.Y.H.acknowledges the support from the National Science Foundation,USA(grant no.CMMI1635443)supported by Querrey Simpson Institute for Bioelectronicssupported by Cancer Center Support Grant P30 CA060553 from the National Cancer Institute awarded to the Robert H.Lurie Comprehensive Cancer Center.
文摘Objective and Impact Statement.Real-time monitoring of the temperatures of regional tissue microenvironments can serve as the diagnostic basis for treating various health conditions and diseases.Introduction.Traditional thermal sensors allow measurements at surfaces or at near-surface regions of the skin or of certain body cavities.Evaluations at depth require implanted devices connected to external readout electronics via physical interfaces that lead to risks for infection and movement constraints for the patient.Also,surgical extraction procedures after a period of need can introduce additional risks and costs.Methods.Here,we report a wireless,bioresorbable class of temperature sensor that exploits multilayer photonic cavities,for continuous optical measurements of regional,deep-tissue microenvironments over a timeframe of interest followed by complete clearance via natural body processes.Results.The designs decouple the influence of detection angle from temperature on the reflection spectra,to enable high accuracy in sensing,as supported by in vitro experiments and optical simulations.Studies with devices implanted into subcutaneous tissues of both awake,freely moving and asleep animal models illustrate the applicability of this technology for in vivo measurements.Conclusion.The results demonstrate the use of bioresorbable materials in advanced photonic structures with unique capabilities in tracking of thermal signatures of tissue microenvironments,with potential relevance to human healthcare.
基金Research in the authors’laboratories was supported in part by research grants from the National Institutes of Health(AT004418,DE020140 to TCH and RRR)the US Department of Defense(OR130096 to JMW)+4 种基金the Scoliosis Research Society(TCH and MJL)the 973 Program of the Ministry of Science and Technology(MOST)of China(#2011CB707906 to TCH)MP and SM were recipients of the Pritzker Summer Research Fellowship funded through the National Institute of Health(NIH)T-35 training grant(NIDDK)#T35DK062719-30The reported work was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430。
文摘Bone tissue regeneration holds the potential to solve both osteoporosis and large skeletal defects,two problems associated with significant morbidity.The differentiation of mesenchymal stem cells into the osteogenic lineage requires a specific microenvironment and certain osteogenic growth factors.Neural EGF Like-Like molecule 1(NELL-1)is a secreted glycoprotein that has proven,both in vitro and in vivo,to be a potent osteo-inductive factor.Furthermore,it has been shown to repress adipogenic differentiation and inflammation.NELL-1 can work synergistically with other osteogenic factors such as Bone Morphogenic Protein(BMP)2 and9,and has shown promise for use in tissue engineering and as a systemically administered drug for the treatment of osteoporosis.Here we provide a comprehensive up-to-date review on the molecular signaling cascade of NELL-1 in mesenchymal stem cells and potential applications in bone regenerative engineering.
基金supported by the Natural Science Foundation of Tianjin(General Program,No.18JCYBJC19500)the Independent Innovation Fund of Tianjin University(No.2019XZS-0014)the Research Grants Council of Hong Kong(No.HKUST615408).
文摘Implant-associated infections are generally difficult to cure owing to the bacterial antibiotic resistance which is attributed to the widespread usage of antibiotics.Given the global threat and increasing influence of antibiotic resistance,there is an urgent demand to explore novel antibacterial strategies other than using antibiotics.Recently,using a certain surface topography to provide a more persistent antibacterial solution attracts more and more attention.However,the clinical application of biomimetic nano-pillar array is not satisfactory,mainly because its antibacterial ability against Gram-positive strain is not good enough.Thus,the pillar array should be equipped with other antibacterial agents to fulfill the bacteriostatic and bactericidal requirements of clinical application.Here,we designed a novel model substrate which was a combination of periodic micro/nano-pillar array and TiO2 for basically understanding the topographical bacteriostatic effects of periodic micro/nano-pillar array and the photocatalytic bactericidal activity of TiO2.Such innovation may potentially exert the synergistic effects by integrating the persistent topographical antibacterial activity and the non-invasive X-ray induced photocatalytic antibacterial property of TiO2 to combat against antibiotic-resistant implant-associated infections.First,to separately verify the topographical antibacterial activity of TiO2 periodic micro/nano-pillar array,we systematically investigated its effects on bacterial adhesion,growth,proliferation,and viability in the dark without involving the photocatalysis of TiO2.The pillar array with sub-micron motif size can significantly inhibit the adhesion,growth,and proliferation of Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli).Such antibacterial ability is mainly attributed to a spatial confinement size-effect and limited contact area availability generated by the special topography of pillar array.Moreover,the pillar array is not lethal to S.aureus and E.coli in 24 h.Then,the X-ray induced photocatalytic antibacterial property of TiO2 periodic micro/nano-pillar array in vitro and in vivo will be systematically studied in a future work.This study could shed light on the direction of surface topography design for future medical implants to combat against antibiotic-resistant implant-associated infections without using antibiotics.
基金The contributing authors’laboratories were supported in part by research grants from the National Institutes of Health(CA226303,DE020140 to TCH and RRR)the U.S.Department of Defense(OR130096 to JMW)+4 种基金the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust(R.R.R.,T.C.H.,and G.A.A.)the Scoliosis Research Society(TCH and MJL),and the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906).This project was also supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430.EC was supported by the Summer Research Program of The University of Chicago Pritzker School of Medicine.TCH was also supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedic Alumni Fund.Funding sources were not involved in the study designin the collection,analysis and interpretation of datain the writing of the reportand in the decision to submit the paper for publication.
文摘With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical treatments.This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient.The most promising potential treatment options rely on stem cellbased therapies.Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function.Clinical approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing capacity.We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential.Given the current problems and complications presented by chronic wounds,we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care.
基金The reported study was supported in part by research grants from the 2019 Chongqing Support Program for Entrepreneurship and Innovation(No.cx2019113)(JF)the 2019 Science and Technology Research Plan Project of Chongqing Education Commission(KJQN201900410)(JF)+9 种基金the 2019 Youth Innovative Talent Training Program of Chongqing Education Commission(No.CY200409)(JF)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)(JF)and the National Key Research and Development Program of China(2016YFC1000803)RRR,TCH and GAA were partially funded by the National Institutes of Health(DE030480)WW was supported by the Medical Scientist Training Program of the National Institutes of Health(T32 GM007281)This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430TCH was also supported by the Mabel Green Myers Research Endowment Fund,The University of Chicago Orthopaedics Alumni Fund,and The University of Chicago SHOCK Fund.Funding sources were not involved in the study designin the collection,analysis and/or interpretation of datain the writing of the reportor in the decision to submit the paper for publication.
文摘Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration.
基金National Research Foundation of Korea(2021R1A6A3A14039205)(Mirae Kim)National Institutes of Health/National Institute of Dental and Craniofacial Research(R01DE030480)(Russell R.Reid).
文摘Approaches to regenerating bone often rely on integrating biomaterials and biological signals in the form of cells or cytokines.However,from a translational point of view,these approaches are challenging due to the sourcing and quality of the biologic,unpredictable immune responses,complex regulatory paths,and high costs.We describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system(CSS)that offers distinct advantages for clinical translation.The CSS comprises a 3D-printed porous polydiolcitrate-hydroxyapatite composite elastomer infused with a polydiolcitrate-graphene oxide hydrogel composite.Using a micro-continuous liquid interface production 3D printer,we fabricate a precise porous ceramic scaffold with 60 wt%hydroxyapatite resembling natural bone.The resulting scaffold integrates with a thermoresponsive hydrogel composite in situ to fit the defect,which is expected to enhance surface contact with surrounding tissue and facilitate biointegration.The antioxidative properties of citrate polymers prevent long-term inflammatory responses.The CSS stimulates osteogenesis in vitro and in vivo.Within 4 weeks in a calvarial critical-sized bone defect model,the CSS accelerated ECM deposition(8-fold)and mineralized osteoid(69-fold)compared to the untreated.Through spatial transcriptomics,we demonstrated the comprehensive biological processes of CSS for prompt osseointegration.Our material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages,potentially expediting clinical application for bone reconstruction surgeries.
基金Center for Advanced Regenerative Engineering and the Department of Urology at the Feinberg School of Medicine at Northwestern University,the Division of Urology at Lurie Children's Hospital of ChicagoNIH grant R01EB026575 to A.K.S.and G.A.A,NIH grant R01DK109539 to A.K.S.,and T32 grant(EB031527)to G.A.A.
文摘Chronic bladder dysfunction due to bladder disease or trauma is detrimental to affected patients as it can lead to increased risk of upper urinary tract dysfunction. Current treatment options include surgical interventions that enlarge the bladder with autologous bowel tissue to alleviate pressure on the upper urinary tract. This highly invasive procedure, termed bladder augmentation enterocystoplasty (BAE), significantly increases the risk of patient morbidity and mortality due to the incompatibility between bowel and bladder tissue. Therefore, patients would significantly benefit from an alternative treatment strategy that can regenerate healthy tissue and restore overall bladder function. Previous research has demonstrated the potential of citrate-based scaffolds co-seeded with bone marrow-derived stem/progenitor cells as an alternative graft for bladder augmentation. Recognizing that contact guidance can potentially influence tissue regeneration, we hypothesized that microtopographically patterned scaffolds would modulate cell responses and improve overall quality of the regenerated bladder tissue. We fabricated microgrooved (MG) scaffolds using the citrate-based biomaterial poly (1,8-octamethylene-citrate-co-octanol) (POCO) and co-seeded them with human bone marrow-derived mesenchymal stromal cells (MSCs) and CD34+ hematopoietic stem/progenitor cells (HSPCs). MG POCO scaffolds supported MSC and HSPC attachment, and MSC alignment within the microgrooves. All scaffolds were characterized and assessed for bladder tissue regeneration in an established nude rat bladder augmentation model. In all cases, normal physiological function was maintained post-augmentation, even without the presence of stem/progenitor cells. Urodynamic testing at 4-weeks post-augmentation for all experimental groups demonstrated that bladder capacity increased and bladder compliance was normal. Histological evaluation of the regenerated tissue revealed that cell-seeded scaffolds restored normal bladder smooth muscle content and resulted in increased revascularization and peripheral nerve regeneration. The presence of microgrooves on the cell-seeded scaffolds increased microvasculature formation by 20 % and urothelial layer thickness by 25 % in the regenerating tissue. Thus, this work demonstrates that microtopography engineering can influence bladder tissue regeneration to improve overall anatomical structure and re-establish bladder physiology.
