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Light(Science & Applications) 2018年第1期7卷 511-523页

作者： Rongrong Liu James A.Winkelmann Graham Spicer Yunxiao Zhu Aya Eid guillermo a.ameer Vadim Backman Ji Yi Department of Biomedical Engineering Northwestern UniversityEvanstonIL 60208USA Department of Chemical and Biological Engineering Northwestern UniversityEvanstonIL 60208USA Department of Medicine Boston University School of MedicineBostonMA 02118USA

Measuring capillary oxygenation and the surrounding ultrastructure can allow one to monitor a microvascular niche and better understand crucial biological ***,capillary oximetry and pericapillary ultrastructure are challenging to measure in *** we demonstrate a novel optical imaging system,dual-band dual-scan inverse spectroscopic optical coherence tomography(D2-ISOCT),that,for the first time,can simultaneously obtain the following metrics in vivo using endogenous contrast:(1)capillary-level oxygen saturation and arteriolar-level blood flow rates,oxygen delivery rates,and oxygen metabolic rates;(2)spatial characteristics of tissue structures at length scales down to 30 nm;and(3)morphological images up to 2mm in *** illustrate the capabilities of D2-ISOCT,we monitored alterations to capillaries and the surrounding pericapillary tissue(tissue between the capillaries)in the healing response of a mouse ear wound *** obtained microvascular and ultrastructural metrics corroborated well with each other,showing the promise of D2-ISOCT for becoming a powerful new non-invasive imaging tool.

关键词： optical capillary inverse

Bone morphogenetic protein-9 effectively induces osteogenic differentiation of reversibly immortalized calvarial mesenchymal progenitor cells

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Genes & Diseases 2015年第3期2卷 268-275页

作者： Chad M.Teven Michael T.Rossi Deana S.Shenaq guillermo a.ameer Russell R.Reid The Laboratory of Craniofacial Development and Biology Section of Plastic and Reconstructive SurgeryUniversity of Chicago MedicineChicagoILUSA Department of Biomedical Engineering Northwestern UniversityChicagoILUSA Department of Surgery Northwestern UniversityChicagoILUSA

Critical-sized craniofacial defect repair represents a significant challenge to reconstructive *** strategies have been employed in an effort to achieve both a functionally and cosmetically acceptable *** morphogenetic proteins(BMPs)provide a robust osteoinductive cue to stimulate bony growth and *** studies have suggested that the BMP-9 isoform is particularly effective in promoting osteogenic differentiation of mesenchymal progenitor *** aim of this study is to characterize the osteogenic capacity of BMP-9 on calvarial mesenchymal progenitor cell *** immortalized murine calvarial progenitor cells(iCALs)were infected with adenoviral vectors encoding BMP-9 or GFP and assessed for early and late stages of osteogenic differentiation in vitro and for osteogenic differentiation via in vivo stem cell implantation *** elevations in alkaline phosphatase(ALP)activity,osteocalcin(OCN)mRNA transcription,osteopontin(OPN)protein expression,and matrix mineralization were detected in BMP-treated cells compared to ***,ALP activity was elevated on days 3,7,9,11,and 13 post-infection and OCN mRNA expression was elevated on days 8,10,and 14 in treated ***,treatment groups demonstrated increased OPN protein expression on day 10 and matrix mineralization on day 14 post-infection relative to control ***-9 also facilitated the formation of new bone in vivo as detailed by gross,microcomputed tomography,and histological ***,we concluded that BMP-9 significantly stimulates osteogenic differentiation in iCALs,and should be considered an effective agent for calvarial tissue regeneration.

关键词： Bone morphogenetic protein(BMP) Bone morphogenetic protein-9(BMP-9) Immortalized calvarial cell(iCAL) Mesenchymal progenitor cell Osteogenic capacity Osteogenic differentiation

A biodegradable microgrooved and tissue mechanocompatible citrate-based scaffold improves bladder tissue regeneration

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Bioactive Materials 2024年第11期41卷 553-563页

作者： Madeleine Goedegebuure Matthew I.Bury Xinlong Wang Pasquale Sanfelice Federico Cammarata Larry Wang Tiffany T.Sharma Nachiket Rajinikanth Vikram Karra Vidhika Siddha Arun K.Sharma guillermo a.ameer Department of Biomedical Engineering Northwestern UniversityEvanstonILUSA Department of Surgery Division of UrologyLurie Children's Hospital of ChicagoChicagoILUSA Department of Urology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Department of Surgery Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Advanced Regenerative Engineering Northwestern UniversityChicagoILUSA International Institute for Nanotechnology Northwestern UniversityChicagoILUSA Simpson Querrey Institute Northwestern UniversityChicagoILUSA Chemistry for Life Processes Institute Northwestern UniversityChicagoILUSA Stanley Manne Children's Research Institute Lurie Children's Hospital of ChicagoChicagoILUSA

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 nor

关键词： Guided bladder tissue regeneration Mesenchymal stem cell Hematopoietic stem cell Microtopography Neovascularization

Stem cells, growth factors and scaffolds in craniofacial regenerative medicine

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Genes & Diseases 2016年第1期3卷 56-71页

作者： Viktor Tollemar Zach J.Collier Maryam K.Mohammed Michael J.Lee guillermo a.ameer Russell R.Reid The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Department of Orthopedic Surgery and Rehabilitation Medicine The University of Chicago Medical CenterChicagoIL 60637USA Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago MedicineChicagoIL 60637USA Department of Surgery Feinberg School of MedicineChicagoIL 60611USA Biomedical Engineering Department Northwestern UniversityEvanstonIL 60208USA

Current reconstructive approaches to large craniofacial skeletal defects are often complicated and ***-sized defects are unable to heal via natural regenerative processes and require surgical intervention,traditionally involving autologous bone(mainly in the form of nonvascularized grafts)or *** bone grafts remain the gold standard of care in spite of the associated risk of donor site *** engineering approaches represent a promising alternative that would serve to facilitate bone regeneration even in large craniofacial skeletal *** strategy has been tested in a myriad of iterations by utilizing a variety of osteoconductive scaffold materials,osteoblastic stem cells,as well as osteoinductive growth factors and small *** of the major challenges facing tissue engineers is creating a scaffold fulfilling the properties necessary for controlled bone *** properties include osteoconduction,osteoinduction,biocompatibility,biodegradability,vascularization,and progenitor cell *** review will provide an overview of how optimization of the aforementioned scaffold parameters facilitates bone regenerative capabilities as well as a discussion of common osteoconductive scaffold materials.

关键词： Bone regeneration Craniofacial defects Osteogenesis Regenerative medicine Scaffolds Tissue engineering

3-D bioprinting technologies in tissue engineering and regenerative medicine:Current and future trends

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Genes & Diseases 2017年第4期4卷 185-195页

作者： Elliot S.Bishop Sami Mostafa Mikhail Pakvasa Hue H.Luu Michael J.Lee Jennifer Moriatis Wolf guillermo a.ameer Tong-Chuan He Russell R.Reid Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago MedicineChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Biomedical Engineering Department Northwestern UniversityEvanstonIL 60208USA Department of Surgery Feinberg School of MedicineNorthwestern UniversityChicagoIL 60616USA

Advances in three-dimensional(3D)printing have increased feasibility towards the synthesis of living *** as 3D bioprinting,this technology involves the precise layering of cells,biologic scaffolds,and growth factors with the goal of creating bioidentical tissue for a variety of *** successes have demonstrated distinct advantages over conventional tissue engineering *** surprisingly,there are current challenges to address before 3D bioprinting becomes clinically *** we provide an overview of 3D bioprinting technology and discuss key advances,clinical applications,and current *** 3D bioprinting is a relatively novel tissue engineering strategy,it holds great potential to play a key role in personalized medicine.

关键词： Additive manufacturing Bioprinting CAD/CAM 3D printing Tissue engineering

Neural EGF-like protein 1(NELL-1):Signaling crosstalk in mesenchymal stem cells and applications in regenerative medicine

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Genes & Diseases 2017年第3期4卷 127-137页

作者： Mikhail Pakvasa Alex Alverdy Sami Mostafa Eric Wang Lucy Fu Alexander Li Leonardo Oliveira Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Tong-Chuan He guillermo a.ameer Russell R.Reid The University of Chicago Pritzker School of MedicineChicagoIL 60637USA Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Rosalind Franklin University Chicago Medical SchoolNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Biomedical Engineering Northwestern UniversityEvanstonIL 60208USA Center for Advanced Regenerative Engineering Northwestern UniversityEvanstonIL 60208USA Department of Surgery Feinberg School of MedicineNorthwestern UniversityChicagoIL 60611USA

Bone tissue regeneration holds the potential to solve both osteoporosis and large skeletal defects,two problems associated with significant *** differentiation of mesenchymal stem cells into the osteogenic lineage requires a specific microenvironment and certain osteogenic growth *** 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 ***,it has been shown to repress adipogenic differentiation and ***-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 *** 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.

关键词： Bone tissue engineering Mesenchymal stem cells NELL-1 NEL-like protein 1 Osteogenic differentiation

Personalized composite scaffolds for accelerated cell-and growth factor-free craniofacial bone regeneration

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Bioactive Materials 2024年第11期41卷 427-439页

作者： Mirae Kim Xinlong Wang Yiming Li Zitong Lin Caralyn P.Collins Yugang Liu Yujin Ahn Hsiu-Ming Tsal Joseph W.Song Chongwen Duan Yi Zhu Cheng Sun Tong-Chuan He Yuan Luo Russell R.Reid guillermo a.ameer Department of Biomedical Engineering Northwestern UniversityEvanstonIL60208USA Center for Advanced Regenerative Engineering Northwestern UniversityEvanstonIL60208USA Department of Preventive Medicine Feinberg School of MedicineNorthwestern UniversityChicagoIL60611USA Department of Mechanical Engineering Northwestern UniversityEvanstonIL60208 USA Department of Chemical and Biomolecular Engineering University of Illinois at Urbana-ChampaignUrbanaIL61820USA Department of Radiology The University of ChicagoChicagoIL60637USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL60637USA Clinical and Translational Sciences Institute Northwestern UniversityChicagoIL60611USA Center for Collaborative AI in Healthcare Institute for AI in MedicineNorthwestern UniversityChicagoIL60611USA Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago Medical CenterChicagoIL60637USA Department of Surgery Feinberg School of MedicineNorthwestern UniversityChicagoIL60611USA Chemistry of Life Process Institute Northwestern UniversityChicagoIL60208USA International Institute for Nanotechnology Northwestern UniversityEvanstonIL60208USA

Approaches to regenerating bone often rely on integrating biomaterials and biological signals in the form of cells or ***,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 *** describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system(CSS)that offers distinct advantages for clinical *** CSS comprises a 3D-printed porous polydiolcitrate-hydroxyapatite composite elastomer infused with a polydiolcitrate-graphene oxide hydrogel *** a micro-continuous liquid interface production 3D printer,we fabricate a precise porous ceramic scaffold with 60 wt%hydroxyapatite resembling natural *** 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 *** antioxidative properties of citrate polymers prevent long-term inflammatory *** CSS stimulates osteogenesis in vitro and in *** 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 *** spatial transcriptomics,we demonstrated the comprehensive biological processes of CSS for prompt *** material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages,potentially expediting clinical application for bone reconstruction surgeries.

关键词： Craniofacial bone regeneration Composite scaffold Material-centric approach3D printing Citrate biomaterial

Reversibly immortalized keratinocytes(iKera)facilitate re-epithelization and skin wound healing:Potential applications in cell-based skin tissue engineering

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Bioactive Materials 2022年第3期7卷 523-540页

作者： Jiamin Zhong Hao Wang Ke Yang Huifeng Wang Chongwen Duan Na Ni Liqin An Yetao Luo Piao Zhao Yannian Gou Shiyan Sheng Deyao Shi Connie Chen William Wagstaff b Bryce Hendren-Santiago b Rex C.Haydon b Hue H.Luu b Russell R.Reid Sherwin HHo guillermo a.ameer Le Shen Tong-Chuan He Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine And Department of Clinical BiochemistrySchool of Laboratory MedicineChongqing Medical UniversityChongqing400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL60637USA The Pediatric Research Institute The Children’s Hospital of Chongqing Medical UniversityChongqing400014China Biomedical Engineering Department Northwestern UniversityEvanstonIL60208USA Department of Orthopaedics Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Surgery The University of Chicago Medical CenterChicagoIL60637USA Center for Advanced Regenerative Engineering(CARE) EvanstonIL60208USA Department of Surgery Northwestern University Feinberg School of MedicineChicagoIL60616USA

Skin injury is repaired through a multi-phase wound healing process of tissue granulation and *** failure in the healing process may lead to chronic non-healing wounds or abnormal scar *** 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 *** are critical to re-epithelialization and wound ***,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound *** first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were *** 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 ***,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.

关键词： Keratinocytes Skin tissue engineering Reversible immortalization SV40 large T antigen PPCN Skin wound healing

Stem cell therapy for chronic skin wounds in the era of personalized medicine:From bench to bedside

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Genes & Diseases 2019年第4期6卷 342-358页

作者： Elam Coalson Elliot Bishop Wei Liu Yixiao Feng Mia Spezia Bo Liu Yi Shen Di Wu Scott Du Alexander J.Li Zhenyu Ye Ling Zhao Daigui Cao Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Rex C.Haydon Lewis Shi Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf guillermo a.ameer Tong-Chuan He Russell R.Reid The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Key Laboratory of Diagnostic Medicine(Ministry of Education) College of Laboratory MedicineChongqing Medical UniversityChongqingChina Department of Orthopaedic Surgery Xiangya Second Hospital of Central South UniversityChangsha 410011China Student Inquiry Research Program Illinois Mathematics and Science Academy(IMSA)AuroraIL60506USA Department of General Surgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215004China Department of Orthopaedic Surgery Chongqing General HospitalChongqing 400013China Department of Biomedical Engineering Northwestern UniversityEvanstonIL 60208USA Department of Surgery Northwestern University Feinberg School of MedicineChicagoIL 60616USA Center for Advanced Regenerative Engineering(CARE) EvanstonIL 60208USA

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 *** requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven *** most promising potential treatment options rely on stem cellbased *** 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 *** approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing *** aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic *** 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.

关键词： Chronic inflammation Chronic wounds Growth factors Personalized medicine Skin Stem cells Wound healing

The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine

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Genes & Diseases 2019年第3期6卷 201-223页

作者： Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf guillermo a.ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago MedicineChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Rosalind Franklin University Chicago Medical SchoolNorth ChicagoIL 60064USA SIR Program Illinois Math and Science Academy(IMSA)AuroraIL 60506USA Department of Biomedical Engineering Northwestern UniversityEvanstonIL60208USA The Department of Surgery Feinberg School of MedicineNorthwestern UniversityChicagoIL60616USA

Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological *** roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ *** of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP *** it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other *** effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of ***,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and *** review aims to summarize our current understanding of BMP9 across biology and the body.

关键词： Adipogenesis Bone morphogenetic proteins(BMPs) BMP9/GDF2 Mesenchymal stem cells(MSCs) Metabolism Osteogenesis Regenerative medicine Tumorigenesis