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REGENERATED ORGANS REGENERATED ORGANS Future Perspectives Edited by C P. S HANDRA HARMA FBSE DepartmentofPharmaceuticalBiotechnology,ManipalCollegeofPharmaceuticalSciences, ManipalUniversity,Manipal,Karnataka CollegeofBiomedicalEngineering&AppliedSciences,PurbanchalUniversity,Kathmandu,Nepal BiomedicalTechnologyWing,SreeChitraTirunalInstituteforMedicalSciences&Technology(SCTIMST), Thiruvananthapuram,India AcademicPressisanimprintofElsevier 125LondonWall,LondonEC2Y5AS,UnitedKingdom 525BStreet,Suite1650,SanDiego,CA92101,UnitedStates 50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom Copyright©2021ElsevierInc.Allrightsreserved. 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Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgeinevaluatingandusingany information,methods,compounds,orexperimentsdescribedherein.Inusingsuchinformationormethodstheyshouldbe mindfuloftheirownsafetyandthesafetyofothers,includingpartiesforwhomtheyhaveaprofessionalresponsibility. Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,assumeanyliabilityforany injuryand/ordamagetopersonsorpropertyasamatterofproductsliability,negligenceorotherwise,orfromanyuseor operationofanymethods,products,instructions,orideascontainedinthematerialherein. BritishLibraryCataloguing-in-PublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress ISBN:978-0-12-821085-7 ForInformationonallAcademicPresspublications visitourwebsiteathttps://www.elsevier.com/books-and-journals Publisher:StacyMasucci AcquisitionsEditor:ElizabethBrown EditorialProjectManager:BillieJeanFernandez ProductionProjectManager:SelvarajRaviraj CoverDesigner:MarkRogers TypesetbyMPSLimited,Chennai,India Contents List of contributors ix 3. Engineered surfaces: A plausible Preface xiii alternative in overviewing critical barriers for reconstructing modern therapeutics or biomimetic scaffolds 1 PreetamGuhaRay,RagaviRajasekaran,TrinaRoy,AbirDutta, Engineering Approaches: From BaisakheeSaha,HemaBora,SubrataK.DasandSantanuDhara Scaffolding to Bioprinting 3.1 Introduction 39 3.2 Currentstatusofmedicaldevicesandrelative Applications complicationsinvolved 40 3.3 Substratesdeployedinbiomedical 1. Tissue and organ regeneration: An applications 41 introduction 3.4 Typesofsurfacemodificationtechniques WilliPaulandChandraP.Sharma towardsligandspecificactivation 44 3.5 Surfaceengineeringofpolymeric 1.1 Introduction 3 substrates 45 1.2 Guidedtissueregeneration 4 3.6 Surfaceactivationofmetallicsubstrates 50 1.3 Stemcellsintissueregeneration 5 3.7 Engineeringorganoids 54 1.4 Conclusionandfutureperspective 8 3.8 Theconceptofengineeredinvivosystem References 8 (organ-on-chipdevices) 57 3.9 Engineeredbactericidalsystems(cid:1)amodern 2. Tissue repair with natural extracellular paradigmtoregenerativemicrodevices 63 matrix (ECM) scaffolds 3.10 Futureperspectivesandchallenges 71 References 71 ThomasChandy 4. Strategies of 3D bioprinting and 2.1 Summary 11 parameters that determine cell interaction 2.2 Background 12 2.3 Smallintestinalsubmucosa 15 with the scaffold - A review 2.4 Acellulardermis 18 GreeshmaRatheesh,CedryckVaquette,PrashantSonarand 2.5 Bladderacellularmatrix 18 YinXiao 2.6 Amnioticmembrane 19 2.7 Pericardiumandfascialata 24 4.1 Introduction 81 2.8 ECMforrepairofdamagedmuscle 26 4.2 Typesofbioprinting 82 2.9 Stemcellsforskeletalmuscle 4.3 Hydrogelsfor3Dbioprinting 85 regeneration 27 4.4 Propertiesofabioink 87 2.10 3Dbioprintingfororganregeneration 27 4.5 Parametersthatdeterminesthecellresponses 2.11 Nanosystemdeliveryofcellularmediators 29 ontissueengineeredscaffold 87 2.12 Perspective 31 4.6 Conclusion 90 References 32 References 91 v vi Contents 5. Multipotent nature of dental pulp stem 7. Engineered cardiac tissue: Concepts and cells for the regeneration of varied future tissues (cid:1) A personalized medicine SoumyaK.Chandrasekhar,FinoshG.Thankam,JoshiC.Ouseph approach andDevendraK.Agrawal V.P.Sivadas,D.P.RahulandPrabhaD.Nair 7.1 Introduction 133 7.2 CardiacECM 134 5.1 Introduction 97 7.3 Post-MIscarring 135 5.2 ImportanceofDPSCsinpersonalized 7.4 Cardiactissueengineering 136 regenerativemedicine 98 7.5 BiomaterialsforCTE 139 5.3 UsefulnessofDPSCsinosteogenicregeneration 7.6 DecellularizedECM 140 therapy 99 7.7 Tissue(cid:1)biomaterialinteraction 140 5.4 DPSCsfortheregenerationofneuronaltissues 7.8 FunctionalmodificationsforCTE andcentralnervoussystem 101 scaffolds 143 5.5 ApplicabilityofDPSCsasastemcellsourcefor 7.9 Bottlenecksandfuture 145 theregenerationofmyocardialandvascular References 146 tissues 102 5.6 Dentalpulpstemcellsasmediatorsofoptic 8. Vascular regeneration and tissue systemregeneration 104 engineering: Progress, clinical impact, and 5.7 RegenerativetherapeuticpotentialofDPSCsin future challenges diabetes 105 5.8 DPSCsasatherapeutictoolforthe SantanuHati,SwatiAgrawalandVikrantRai regenerationofcartilageandtendon 106 5.9 Futureperspectivesandconclusions 108 8.1 Introduction 153 References 114 8.2 Regenerativetherapies 155 8.3 Conclusionandfuturedirections 162 References 163 2 3 Cardiovascular System Musculoskeletal Regeneration of 6. Regenerating the heart: The past, present, & future Tissues AdityaSenguptaandRaghavA.Murthy 9. Oral tissue regeneration: Current status 6.1 Introduction 121 and future perspectives 6.2 Cardiomyocyteregenerative MajiJose,VrindaRajagopalandFinoshG.Thankam potential 122 6.3 Cell-basedstrategies 122 9.1 Introduction 169 6.4 Cardiacstemcells 123 9.2 Histologyoforaltissues 169 6.5 Pluripotentstemcells 123 9.3 Oralmicrobiologyinhealthanddiseases 170 6.6 Cell-freestrategies 124 9.4 Oraldiseases,prevalenceand 6.7 Growthfactors 124 management 171 6.8 Exosomes&microRNAtechnology 124 9.5 Oralmucosallesions 173 6.9 Directreprogramming 125 9.6 Oralcancer 174 6.10 Endogenousrepair&regeneration 126 9.7 Oro-dentaltissueengineering:amodern 6.11 Thefuture 127 epochintoothmanagement 175 6.12 Conclusion 128 9.8 Strategiesadaptedforperiodontaltissue References 128 regeneration 177 Contents vii 9.9 ECMregenerationwithECM-based 12.3 Engineeringapproaches(scaffolds) 263 scaffolds 177 12.4 Summary 265 9.10 Biomaterialscaffoldsfororo-dentaltissue 12.5 Futureperspective 268 regeneration 178 References 269 9.11 Stemcellbiologyupdatesfororo-dentaltissue regeneration 180 9.12 Summary 182 References 182 4 Furtherreading 187 Regenerative Neuroscience 10. Regenerative technologies for oral structures 13. Recent developments and new potentials for neuroregeneration PrachiHanwatkarandAjayKashi SreekanthSreekumaran,AnithaRadhakrishnanandSanjuP.Joy 10.1 Introduction 189 10.2 Embryologyoforalstructures 190 13.1 Nervoussystem,neurodegenerationand 10.3 Regenerationofteeth 190 regeneration(cid:1)anutshell 278 10.4 Regenerationofmuscles/tongue 194 13.2 Strategiesforneuralregenerationand 10.5 Regenerationofbone 195 repair 281 10.6 RegenerationofTMJ 196 13.3 Futureperspectives 285 10.7 Regenerationofsalivaryglands 196 References 285 10.8 Microgravity 197 10.9 Ethicalconsiderations 198 References 198 5 11. State-of-the-art strategies and future interventions in bone and Respiratory Research cartilage repair for personalized 14. Lung disease and repair (cid:1) Is regenerative therapy regeneration the answer? YogendraPratapSingh,JosephChristakiranMoses,Ashutosh Bandyopadhyay,BibritaBhar,BhaskarBirru,NandanaBhardwaj S.S.PradeepKumarandA.MayaNandkumar andBimanB.Mandal 14.1 Embryonicdevelopment 293 11.1 Introduction 203 14.2 Stemcellsinthelung 294 11.2 State-of-the-artstrategiesfor 14.3 Epithelial(cid:1)mesenchymalinteractions 295 regeneration 205 14.4 Roleofmechanicalforcesinlung 11.3 Diseasemodels 223 architecture 296 11.4 Graftsubstitutes 229 14.5 Lungregenerationindisease 296 11.5 Clinicalstatus 232 14.6 Invivo(cid:1)Animalmodels 297 11.6 Conclusionandfutureperspectives 237 14.7 Invitromodels 297 Acknowledgment 239 14.8 Lung-on-achip(LOC)model 298 References 239 14.9 Threedimensionalprintingofthe lung 299 12. Muscle tissue engineering (cid:1) A 14.10 Futureperspectiveslatest4D materials perspective printing 299 Acknowledgments 299 JohnP.Bradford,GerardoHernandez-MorenoandVinoyThomas Conflictofinterest 300 12.1 Introduction 249 References 300 12.2 Bio-interfacingmaterials 254 Furtherreading 301 viii Contents 6 16. Role of umbilical cord stem cells in tissue engineering Key Enabling Technologies for MerlinRajeshLalandOormilaKovilam Regenerative Medicine Future 16.1 UmbilicalcordandMSCs 332 Outlook and Conclusions 16.2 TransplantationbiologyofUCMSCs: biomaterials,differentiationand 15. 3D printing in regenerative medicine regeneration 332 AynurUnalandNidhiArora 16.3 Concernsandperspective 335 References 336 15.1 Introduction 305 15.2 Conclusions 326 Index 339 References 327 List of contributors Devendra K. Agrawal Department of Thomas Chandy Phillips Medisize LLC, TranslationalResearch,WesternUniversityof Hudson,WI,UnitedStates HealthSciences,Pomona,CA,UnitedStates Subrata K. Das Biomaterials and Tissue Swati Agrawal Department of Surgery, Engineering Laboratory, School of Medical Creighton University School of Medicine, ScienceandTechnology(SMST),IndianInstitute Omaha,NE,UnitedStates ofTechnology(cid:1)Kharagpur,Kharagpur,India NidhiArora SSInfotech,Indore,MP,India Santanu Dhara Biomaterials and Tissue Ashutosh Bandyopadhyay Biomaterial and Engineering Laboratory, School of Medical Tissue Engineering Laboratory, Department of Science and Technology (SMST), Indian BiosciencesandBioengineering,IndianInstitute Institute of Technology (cid:1) Kharagpur, ofTechnologyGuwahati,Guwahati,India Kharagpur,India BibritaBhar BiomaterialandTissueEngineering AbirDutta BiomaterialsandTissueEngineering Laboratory, Department of Biosciences and Laboratory, School of Medical Science and Bioengineering, Indian Institute of Technology Technology (SMST), Indian Institute of Guwahati,Guwahati,India Technology(cid:1)Kharagpur,Kharagpur,India Nandana Bhardwaj Department of PrachiHanwatkar RochesterGeneralHospital, Biotechnology, National Institute of Rochester,NY,UnitedStates Pharmaceutical Education and Research Santanu Hati Department of Biomedical Guwahati,Guwahati,India Science, Creighton University School of Bhaskar Birru Biomaterial and Tissue Medicine,Omaha,NE,UnitedStates Engineering Laboratory, Department of Gerardo Hernandez-Moreno Polymers & BiosciencesandBioengineering,IndianInstitute ofTechnologyGuwahati,Guwahati,India Healthcare Materials/Devices, Department of Materials Science & Engineering University Hema Bora BiomaterialsandTissueEngineering of Alabama at Birmingham (UAB), Laboratory, School of Medical Science and Birmingham,AL,UnitedStates Technology (SMST), Indian Institute of Technology(cid:1)Kharagpur,Kharagpur,India Maji Jose Department of Oral Pathology & Microbiology, Yenepoya Dental College, John P. Bradford Polymers & Healthcare Yenepoya (Deemed to be University), Materials/Devices, Department of Materials Mangalore,India Science&EngineeringUniversityofAlabama Sanju P. Joy Neurology, National Institute of at Birmingham (UAB), Birmingham, AL, UnitedStates Mental Health and Neuro-Sciences, Bangalore, India Soumya K. Chandrasekhar Department of Zoology, KKTM Government College, Pullut, Ajay Kashi Private Practice, Rochester, NY, Calicut University, Kerala, India; Department UnitedStates of Zoology, Christ College, Irinjalakuda, Oormila Kovilam St Joseph’s Hospital, CalicutUniversity,Kerala,India Indiana,UnitedStates ix x Listofcontributors Merlin Rajesh Lal LifeCell International (Pvt) Vikrant Rai Department of Biomedical Ltd,Chennai,India Science, Creighton University School of Biman B. Mandal Biomaterial and Tissue Medicine,Omaha,NE,UnitedStates Engineering Laboratory, Department of Vrinda Rajagopal Department of Biosciences and Bioengineering, Indian Biochemistry, University of Kerala, Institute of Technology Guwahati, Guwahati, Karyavattom,India India; Centre for Nanotechnology, Indian Ragavi Rajasekaran Biomaterials and Tissue Institute of Technology Guwahati, Guwahati, Engineering Laboratory, School of Medical India Science and Technology (SMST), Indian A. Maya Nandkumar Division of Microbial Institute of Technology (cid:1) Kharagpur, Technology, Sree Chitra Tirunal Institute for Kharagpur,India Medical Sciences & Technology Greeshma Ratheesh Institute of Health and Thiruvananthapuram,India Biomedical Innovation, Queensland University Joseph Christakiran Moses Biomaterial and ofTechnology,Brisbane,QLD,Australia Tissue Engineering Laboratory, Department Preetam Guha Ray Biomaterials and Tissue of Biosciences and Bioengineering, Indian Engineering Laboratory, School of Medical Institute of Technology Guwahati, Guwahati, Science and Technology (SMST), Indian India Institute of Technology (cid:1) Kharagpur, Raghav A. Murthy Department of Kharagpur,India Cardiovascular Surgery, Icahn School of Trina Roy Biomaterials and Tissue Medicine at Mount Sinai, New York, NY, Engineering Laboratory, School of Medical UnitedStates Science and Technology (SMST), Indian PrabhaD.Nair DivisionofTissueEngineering Institute of Technology (cid:1) Kharagpur, and Regeneration Technologies, Biomedical Kharagpur,India Technology Wing, Sree Chitra Tirunal Baisakhee Saha Biomaterials and Tissue Institute for Medical Sciences and Engineering Laboratory, School of Medical Technology (SCTIMST), Poojapura, Science and Technology (SMST), Indian Thiruvananthapuram,India Institute of Technology (cid:1) Kharagpur, Joshi C. Ouseph Department of Zoology, Kharagpur,India Christ College, Irinjalakuda, Calicut AdityaSengupta DepartmentofCardiovascular University,Kerala,India Surgery, Icahn School of Medicine at Mount Willi Paul Biomedical Technology Wing, Sree Sinai,NewYork,NY,UnitedStates Chitra Tirunal Institute for Medical Sciences Chandra P. Sharma Biomedical Technology &Technology,Thiruvananthapuram,India Wing, Sree Chitra Tirunal Institute for S.S. Pradeep Kumar Division of Microbial Medical Sciences & Technology, Technology, Sree Chitra Tirunal Institute for Thiruvananthapuram,India Medical Sciences & Technology Yogendra Pratap Singh BiomaterialandTissue Thiruvananthapuram,India Engineering Laboratory, Department of Anitha Radhakrishnan Research and BiosciencesandBioengineering,IndianInstitute Development Department, Pharmaceutical ofTechnologyGuwahati,Guwahati,India Corporation (Indian Medicine), Thrissur, V.P. Sivadas Division of Tissue Engineering India and Regeneration Technologies, Biomedical D.P. Rahul Department of Orthodontics and Technology Wing, Sree Chitra Tirunal Dentofacial Orthopedics, School of Dentistry, Institute for Medical Sciences and Amrita Vishwa Vidyapeetham, Amrita Technology (SCTIMST), Poojapura, InstituteofMedicalSciences,Kochi,India Thiruvananthapuram,India Listofcontributors xi Prashant Sonar School of Chemistry and Aynur Unal Digital Monzoukuri, Palo Alto, Physics, Queensland University of CA,UnitedStates Technology,Brisbane,QLD,Australia Cedryck Vaquette School of Dentistry, The Sreekanth Sreekumaran Department of University of Queensland, Brisbane, QLD, Biochemistry, University of Kerala, Australia Thiruvananthapuram,India Yin Xiao Institute of Health and Biomedical Finosh G. Thankam Department of Innovation, Queensland University of TranslationalResearch,WesternUniversityof Technology, Brisbane, QLD, Australia; HealthSciences,Pomona,CA,UnitedStates Australia-China Centre for Tissue Vinoy Thomas Polymers & Healthcare Engineering and Regenerative Medicine, Materials/Devices, Department of Materials Centre for Biomedical Technologies, Queensland University of Technology, Science&EngineeringUniversityofAlabama Brisbane,QLD,Australia at Birmingham (UAB), Birmingham, AL, UnitedStates