Multi-Functional Macromers for Hydrogel Design in Biomedical Engineering and Regenerative Medicine

Contemporary biomaterials are expected to provide tailored mechanical, biological and structural cues to encapsulated or invading cells in regenerative applications. In addition, the degradative properties of the material also have to be adjustable to the desired application. Oligo- or polymeric building blocks that can be further cross-linked into hydrogel networks, here addressed as macromers, appear as the prime option to assemble gels with the necessary degrees of freedom in the adjustment of the mentioned key parameters. Recent developments in the design of multi-functional macromers with two or more chemically different types of functionalities are summarized and discussed in this review illustrating recent trends in the development of advanced hydrogel building blocks for regenerative applications.

[1]  Zu-wei Ma,et al.  Protein-reactive, thermoresponsive copolymers with high flexibility and biodegradability. , 2008, Biomacromolecules.

[2]  Yunxiao Liu,et al.  A biomimetic hydrogel based on methacrylated dextran-graft-lysine and gelatin for 3D smooth muscle cell culture. , 2010, Biomaterials.

[3]  M. Radisic,et al.  Photocrosslinkable hydrogel for myocyte cell culture and injection. , 2007, Journal of biomedical materials research. Part B, Applied biomaterials.

[4]  Jason S. Lewis,et al.  The Growing Impact of Bioorthogonal Click Chemistry on the Development of Radiopharmaceuticals , 2013, The Journal of Nuclear Medicine.

[5]  Antonios G Mikos,et al.  Synthesis and characterization of dual stimuli responsive macromers based on poly(N-isopropylacrylamide) and poly(vinylphosphonic acid). , 2010, Biomacromolecules.

[6]  Takehisa Matsuda,et al.  The potential of poly(N-isopropylacrylamide) (PNIPAM)-grafted hyaluronan and PNIPAM-grafted gelatin in the control of post-surgical tissue adhesions. , 2005, Biomaterials.

[7]  T. Osaki,et al.  Chitin, Chitosan, and Its Derivatives for Wound Healing: Old and New Materials , 2015, Journal of functional biomaterials.

[8]  A. Lowe,et al.  Thiol-ene “click” reactions and recent applications in polymer and materials synthesis , 2010 .

[9]  C. Werner,et al.  Neurotropic growth factors and glycosaminoglycan based matrices to induce dopaminergic tissue formation. , 2015, Biomaterials.

[10]  Wesley R. Legant,et al.  Bioactive hydrogels made from step-growth derived PEG-peptide macromers. , 2010, Biomaterials.

[11]  Kristi S. Anseth,et al.  Coumarin-Based Photodegradable Hydrogel: Design, Synthesis, Gelation, and Degradation Kinetics. , 2014, ACS macro letters.

[12]  Patrick T. Mather,et al.  Review of progress in shape-memory polymers , 2007 .

[13]  April M. Kloxin,et al.  Design of Thiol- and Light-sensitive Degradable Hydrogels using Michael-type Addition Reactions. , 2015, Polymer chemistry.

[14]  Dong-An Wang,et al.  An improved injectable polysaccharide hydrogel: modified gellan gum for long-term cartilage regeneration in vitro , 2009 .

[15]  A. Kasko,et al.  Photodegradable macromers and hydrogels for live cell encapsulation and release. , 2012, Journal of the American Chemical Society.

[16]  G. Abraham,et al.  Crosslinkable PEO-PPO-PEO-based reverse thermo-responsive gels as potentially injectable materials , 2003, Journal of biomaterials science. Polymer edition.

[17]  C. Werner,et al.  Biohybrid networks of selectively desulfated glycosaminoglycans for tunable growth factor delivery. , 2014, Biomacromolecules.

[18]  Junmin Zhu,et al.  Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. , 2010, Biomaterials.

[19]  Shaoyu Lü,et al.  Thermoresponsive injectable hydrogel for three-dimensional cell culture: chondroitin sulfate bioconjugated with poly(N-isopropylacrylamide) synthesized by RAFT polymerization , 2011 .

[20]  Mrityunjoy Kar,et al.  Smart hydrogels as functional biomimetic systems. , 2014, Biomaterials science.

[21]  Jian Yang,et al.  A thermoresponsive biodegradable polymer with intrinsic antioxidant properties. , 2014, Biomacromolecules.

[22]  Erkki Ruoslahti,et al.  Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule , 1984, Nature.

[23]  R. Zhuo,et al.  Synthesis of thermosensitive P(NIPAAm-co-HEMA)/cellulose hydrogels via “click” chemistry , 2009 .

[24]  Robert Stern,et al.  Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications , 2006, Biotechnology Letters.

[25]  April M. Kloxin,et al.  Dually degradable click hydrogels for controlled degradation and protein release. , 2014, Journal of materials chemistry. B.

[26]  Alyssa Panitch,et al.  Biologically engineered protein-graft-poly(ethylene glycol) hydrogels: a cell adhesive and plasmin-degradable biosynthetic material for tissue repair. , 2002, Biomacromolecules.

[27]  D. Mooney,et al.  Hydrogels for tissue engineering: scaffold design variables and applications. , 2003, Biomaterials.

[28]  B. Mattiasson,et al.  Smart polymers for bioseparation and bioprocessing , 2002 .

[29]  Yuhan Lee,et al.  Thermo-sensitive, injectable, and tissue adhesive sol–gel transition hyaluronic acid/pluronic composite hydrogels prepared from bio-inspired catechol-thiol reaction , 2010 .

[30]  J. Hubbell,et al.  Protein delivery from materials formed by self-selective conjugate addition reactions. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[31]  F. Caruso,et al.  Photoinitiated alkyne-azide click and radical cross-linking reactions for the patterning of PEG hydrogels. , 2012, Biomacromolecules.

[32]  R. Langer,et al.  Light-induced shape-memory polymers , 2005, Nature.

[33]  J. Guan,et al.  Regulating myogenic differentiation of mesenchymal stem cells using thermosensitive hydrogels. , 2015, Acta biomaterialia.

[34]  S. Bellis,et al.  Advantages of RGD peptides for directing cell association with biomaterials. , 2011, Biomaterials.

[35]  G. Prestwich,et al.  The translational imperative: making cell therapy simple and effective. , 2012, Acta biomaterialia.

[36]  M. Becker,et al.  Strain-Promoted Crosslinking of PEG-based Hydrogels via Copper-Free Cycloaddition. , 2012, ACS macro letters.

[37]  B. Lee,et al.  Comparison of properties between NIPAAm-based simultaneously physically and chemically gelling polymer systems for use in vivo. , 2012, Acta biomaterialia.

[38]  K. Na,et al.  Phenotype of Hepatocyte Spheroids Behavior within Thermo-Sensitive Poly(NiPAAm-co-PEG-g-GRGDS) Hydrogel as a Cell Delivery Vehicle , 2005, Biotechnology Letters.

[39]  Kinam Park,et al.  Smart Polymeric Gels: Redefining the Limits of Biomedical Devices. , 2007, Progress in polymer science.

[40]  Robert Liska,et al.  Vinyl carbonates, vinyl carbamates, and related monomers: synthesis, polymerization, and application. , 2012, Chemical Society reviews.

[41]  J. Rubin,et al.  Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering. , 2009, Biomaterials.

[42]  Antonios G Mikos,et al.  Three-dimensional culture of differentiating marrow stromal osteoblasts in biomimetic poly(propylene fumarate-co-ethylene glycol)-based macroporous hydrogels. , 2003, Journal of biomedical materials research. Part A.

[43]  A. Salgado,et al.  Angiogenic potential of gellan-gum-based hydrogels for application in nucleus pulposus regeneration: in vivo study. , 2012, Tissue engineering. Part A.

[44]  Y. Nakayama,et al.  Thermoresponsive artificial extracellular matrix for tissue engineering: hyaluronic acid bioconjugated with poly(N-isopropylacrylamide) grafts. , 2001, Biomacromolecules.

[45]  Y. Bae,et al.  Thermosensitive sol-gel reversible hydrogels. , 2002, Advanced drug delivery reviews.

[46]  A. Mikos,et al.  Synthesis and characterization of injectable, thermally and chemically gelable, amphiphilic poly(N-isopropylacrylamide)-based macromers. , 2008, Biomacromolecules.

[47]  J. Hubbell,et al.  Enhanced proteolytic degradation of molecularly engineered PEG hydrogels in response to MMP-1 and MMP-2. , 2010, Biomaterials.

[48]  C. van Nostrum,et al.  Novel crosslinking methods to design hydrogels. , 2002, Advanced drug delivery reviews.

[49]  J. Hubbell,et al.  Synthesis and physicochemical characterization of end-linked poly(ethylene glycol)-co-peptide hydrogels formed by Michael-type addition. , 2003, Biomacromolecules.

[50]  Gabriela A Silva,et al.  Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. , 2007, Advanced drug delivery reviews.

[51]  Yasuhiko Tabata,et al.  Biomaterial technology for tissue engineering applications , 2009, Journal of The Royal Society Interface.

[52]  Jennifer H Elisseeff,et al.  Synthesis and characterization of a novel degradable phosphate-containing hydrogel. , 2003, Biomaterials.

[53]  Antonios G Mikos,et al.  Biomimetic materials for tissue engineering. , 2003, Biomaterials.

[54]  Michelle C LaPlaca,et al.  Thermoreversible laminin-functionalized hydrogel for neural tissue engineering. , 2006, Journal of biomedical materials research. Part A.

[55]  A. Beck‐Sickinger,et al.  Biocompatible silicon surfaces through orthogonal click chemistries and a high affinity silicon oxide binding peptide. , 2012, Bioconjugate chemistry.

[56]  J. Fisher,et al.  Synthesis of poly(propylene fumarate) , 2009, Nature Protocols.

[57]  J. Suh,et al.  Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. , 2000, Biomaterials.

[58]  Aleksandr Ovsianikov,et al.  Additive manufacturing of photosensitive hydrogels for tissue engineering applications , 2014 .

[59]  A. Weiss,et al.  Elastin based cell-laden injectable hydrogels with tunable gelation, mechanical and biodegradation properties. , 2014, Biomaterials.

[60]  R. L. Reis,et al.  Gellan gum‐based hydrogels for intervertebral disc tissue‐engineering applications , 2011, Journal of tissue engineering and regenerative medicine.

[61]  R. Zhuo,et al.  “Click” chemistry for in situ formation of thermoresponsive P(NIPAAm‐co‐HEMA)‐based hydrogels , 2008 .

[62]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[63]  Malar A. Azagarsamy,et al.  Synthetically Tractable Click Hydrogels for Three-Dimensional Cell Culture Formed Using Tetrazine–Norbornene Chemistry , 2013, Biomacromolecules.

[64]  S. Ghanaati,et al.  Biological performance of cell‐encapsulated methacrylated gellan gum‐based hydrogels for nucleus pulposus regeneration , 2017, Journal of tissue engineering and regenerative medicine.

[65]  M. Guo,et al.  Reactive macromolecular micelle crosslinked highly elastic hydrogel with water-triggered shape-memory behaviour , 2014 .

[66]  D. Vigetti,et al.  Hyaluronan: biosynthesis and signaling. , 2014, Biochimica et biophysica acta.

[67]  A. Khademhosseini,et al.  Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology , 2006 .

[68]  Y. Sohn,et al.  Thermogelling poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) disulfide multiblock copolymer as a thiol-sensitive degradable polymer. , 2006, Biomacromolecules.

[69]  T. Muir,et al.  Synthesis of proteins by native chemical ligation. , 1994, Science.

[70]  M. Hacker,et al.  Reactive and stimuli-responsive maleic anhydride containing macromers – multi-functional cross-linkers and building blocks for hydrogel fabrication , 2013 .

[71]  H. Maynard,et al.  Synthesis of photodegradable macromers for conjugation and release of bioactive molecules. , 2013, Biomacromolecules.

[72]  Hai-Bo Zhao,et al.  Multi-stimuli sensitive supramolecular hydrogel formed by host–guest interaction between PNIPAM-Azo and cyclodextrin dimers , 2014 .

[73]  Jay C. Sy,et al.  Maleimide Cross‐Linked Bioactive PEG Hydrogel Exhibits Improved Reaction Kinetics and Cross‐Linking for Cell Encapsulation and In Situ Delivery , 2012, Advanced materials.

[74]  Takehisa Matsuda,et al.  Poly(N-isopropylacrylamide)-grafted gelatin as a thermoresponsive cell-adhesive, mold-releasable material for shape-engineered tissues , 2004, Journal of biomaterials science. Polymer edition.

[75]  Daniel Cohn,et al.  Ethoxysilane-capped PEO-PPO-PEO triblocks: a new family of reverse thermo-responsive polymers. , 2004, Biomaterials.

[76]  Wenguang Liu,et al.  Dipole–Dipole and H‐Bonding Interactions Significantly Enhance the Multifaceted Mechanical Properties of Thermoresponsive Shape Memory Hydrogels , 2015 .

[77]  Thrimoorthy Potta,et al.  Chemically crosslinkable thermosensitive polyphosphazene gels as injectable materials for biomedical applications. , 2009, Biomaterials.

[78]  A. Mikos,et al.  Structure-property evaluation of thermally and chemically gelling injectable hydrogels for tissue engineering. , 2012, Biomacromolecules.

[79]  A. Mikos,et al.  Chapter 33 – Synthetic Polymers , 2011 .

[80]  Andrew Wilkinson Compendium of Chemical Terminology , 1997 .

[81]  Kristi S. Anseth,et al.  Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments , 2009 .

[82]  Yoshihito Osada,et al.  Shape memory in hydrogels , 1995, Nature.

[83]  A. Mikos,et al.  Synthesis, physicochemical characterization, and cytocompatibility of bioresorbable, dual-gelling injectable hydrogels. , 2014, Biomacromolecules.

[84]  Horst Kessler,et al.  RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. , 2003, Biomaterials.

[85]  A. Mikos,et al.  Synthesis of in situ cross-linkable macroporous biodegradable poly(propylene fumarate-co-ethylene glycol) hydrogels. , 2002, Biomacromolecules.

[86]  T. Matsuda,et al.  Tissue-engineered cartilage using an injectable and in situ gelable thermoresponsive gelatin: fabrication and in vitro performance. , 2003, Tissue engineering.

[87]  Eunhee Cho,et al.  Formulation and characterization of poloxamine-based hydrogels as tissue sealants. , 2012, Acta biomaterialia.

[88]  C. Werner,et al.  Modular StarPEG-Heparin Gels with Bifunctional Peptide Linkers. , 2010, Macromolecular rapid communications.

[89]  A. Mikos,et al.  Cytocompatibility evaluation of amphiphilic, thermally responsive and chemically crosslinkable macromers for in situ forming hydrogels. , 2009, Biomaterials.

[90]  Jun Wang,et al.  Biodegradable and photocrosslinkable polyphosphoester hydrogel. , 2006, Biomaterials.

[91]  J. Hubbell,et al.  Conjugate addition reactions combined with free-radical cross-linking for the design of materials for tissue engineering. , 2001, Biomacromolecules.

[92]  Brian Derby,et al.  Inkjet printing and cell seeding thermoreversible photocurable gel structures , 2011 .

[93]  N. Peppas,et al.  Hydrogels in Pharmaceutical Formulations , 1999 .

[94]  J. Fisher,et al.  Thermoreversible hydrogel scaffolds for articular cartilage engineering. , 2004, Journal of biomedical materials research. Part A.

[95]  Chaenyung Cha,et al.  25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine , 2014, Advanced materials.

[96]  Jessica L. Nichol,et al.  Polyphosphazenes with amino acid citronellol ester side groups for biomedical applications , 2015 .

[97]  Timothy E. Long,et al.  Michael addition reactions in macromolecular design for emerging technologies , 2006 .

[98]  Jianshu Li,et al.  Thermoresponsive hydrogels from phosphorylated ABA triblock copolymers: a potential scaffold for bone tissue engineering. , 2013, Biomacromolecules.

[99]  T. L. Deans,et al.  Stem cells in musculoskeletal engineered tissue. , 2009, Current opinion in biotechnology.

[100]  Mark W. Tibbitt,et al.  Responsive culture platform to examine the influence of microenvironmental geometry on cell function in 3D. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[101]  Sang-Hyug Park,et al.  Synthesis of Arg–Gly–Asp (RGD) Sequence Conjugated Thermo-Reversible Gel via the PEG Spacer Arm as an Extracellular Matrix for a Pheochromocytoma Cell (PC12) Culture , 2004, Bioscience, biotechnology, and biochemistry.

[102]  David J. Mooney,et al.  Growth Factors, Matrices, and Forces Combine and Control Stem Cells , 2009, Science.

[103]  Zhiyuan Zhong,et al.  Click hydrogels, microgels and nanogels: emerging platforms for drug delivery and tissue engineering. , 2014, Biomaterials.

[104]  F. Kurtis Kasper,et al.  Synthesis and Characterization of Injectable, Biodegradable, Phosphate-Containing, Chemically Cross-Linkable, Thermoresponsive Macromers for Bone Tissue Engineering , 2014, Biomacromolecules.

[105]  Alexander Chan,et al.  Remote and local control of stimuli responsive materials for therapeutic applications. , 2013, Advanced drug delivery reviews.

[106]  A. Mikos,et al.  In vitro and in vivo evaluation of self-mineralization and biocompatibility of injectable, dual-gelling hydrogels for bone tissue engineering. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[107]  Christopher N Bowman,et al.  Thiol-ene click chemistry. , 2010, Angewandte Chemie.

[108]  T. Vermonden,et al.  Thermogelling and Chemoselectively Cross-Linked Hydrogels with Controlled Mechanical Properties and Degradation Behavior. , 2015, Biomacromolecules.

[109]  Jason A Burdick,et al.  Hydrolytically degradable hyaluronic acid hydrogels with controlled temporal structures. , 2008, Biomacromolecules.

[110]  Kristi S Anseth,et al.  Advances in bioactive hydrogels to probe and direct cell fate. , 2012, Annual review of chemical and biomolecular engineering.

[111]  Quang Vinh Nguyen,et al.  Injectable polymeric hydrogels for the delivery of therapeutic agents: A review , 2015 .

[112]  W. M. Huang,et al.  Shaping tissue with shape memory materials. , 2013, Advanced drug delivery reviews.

[113]  Kristi S. Anseth,et al.  Cytocompatible Click-based Hydrogels with Dynamically-Tunable Properties Through Orthogonal Photoconjugation and Photocleavage Reactions , 2011, Nature chemistry.

[114]  Fan Yang,et al.  Photo‐crosslinkable PEG‐Based Microribbons for Forming 3D Macroporous Scaffolds with Decoupled Niche Properties , 2014, Advanced materials.

[115]  M. Hacker,et al.  Gelatin-based biomaterial engineering with anhydride-containing oligomeric cross-linkers. , 2014, Biomacromolecules.

[116]  D. Nair,et al.  The Thiol-Michael Addition Click Reaction: A Powerful and Widely Used Tool in Materials Chemistry , 2014 .

[117]  T. Matsuda,et al.  System-engineered cartilage using poly(N-isopropylacrylamide)-grafted gelatin as in situ-formable scaffold: in vivo performance. , 2003, Tissue engineering.

[118]  A. Mikos,et al.  Synthesis and characterization of triblock copolymers of methoxy poly(ethylene glycol) and poly(propylene fumarate). , 2002, Biomacromolecules.

[119]  Antonios G Mikos,et al.  Biodegradable, phosphate-containing, dual-gelling macromers for cellular delivery in bone tissue engineering. , 2015, Biomaterials.

[120]  C. Chu,et al.  Synthesis and characterization of partially biodegradable, temperature and pH sensitive Dex-MA/PNIPAAm hydrogels. , 2004, Biomaterials.

[121]  M. Tamura,et al.  Click-crosslinkable and photodegradable gelatin hydrogels for cytocompatible optical cell manipulation in natural environment , 2015, Scientific Reports.

[122]  Ali Khademhosseini,et al.  Modified Gellan Gum hydrogels with tunable physical and mechanical properties. , 2010, Biomaterials.

[123]  S. Bryant,et al.  Thermoresponsive, in situ cross-linkable hydrogels based on N-isopropylacrylamide: fabrication, characterization and mesenchymal stem cell encapsulation. , 2011, Acta biomaterialia.

[124]  C. V. van Blitterswijk,et al.  Evaluation of photocrosslinked Lutrol hydrogel for tissue printing applications. , 2009, Biomacromolecules.

[125]  M. Shoichet,et al.  Regenerative biomaterials that "click": simple, aqueous-based protocols for hydrogel synthesis, surface immobilization, and 3D patterning. , 2011, Bioconjugate chemistry.

[126]  Howard G. Schild,et al.  Microcalorimetric detection of lower critical solution temperatures in aqueous polymer solutions , 1990 .

[127]  Jian Yang,et al.  Citrate-based Biodegradable Injectable hydrogel Composites for Orthopedic Applications. , 2013, Biomaterials science.

[128]  R. Pelton,et al.  Temperature-sensitive aqueous microgels. , 2000, Advances in colloid and interface science.

[129]  S. Danishefsky,et al.  Oxo-ester mediated native chemical ligation: concept and applications. , 2008, Journal of the American Chemical Society.

[130]  U. Anderegg,et al.  More than just a filler – the role of hyaluronan for skin homeostasis , 2014, Experimental dermatology.

[131]  Kinam Park,et al.  Environment-sensitive hydrogels for drug delivery. , 2001, Advanced drug delivery reviews.

[132]  T. Hoare,et al.  Injectable, Degradable Thermoresponsive Poly(N-isopropylacrylamide) Hydrogels. , 2012, ACS macro letters.

[133]  Larry L Hench,et al.  Third-Generation Biomedical Materials , 2002, Science.

[134]  Nicholas A Peppas,et al.  Multi-responsive hydrogels for drug delivery and tissue engineering applications , 2014, Regenerative biomaterials.

[135]  T. Hoare,et al.  Tuning gelation time and morphology of injectable hydrogels using ketone-hydrazide cross-linking. , 2014, Biomacromolecules.

[136]  P. Messersmith,et al.  Hydrogels cross-linked by native chemical ligation. , 2009, Biomacromolecules.

[137]  A. Mikos,et al.  Synthesis of oligo(poly(ethylene glycol) fumarate) , 2012, Nature Protocols.

[138]  V. Khutoryanskiy,et al.  Biomedical applications of hydrogels: A review of patents and commercial products , 2015 .

[139]  A. Mikos,et al.  Synthesis and characterization of thermally and chemically gelling injectable hydrogels for tissue engineering. , 2012, Biomacromolecules.

[140]  Erhan Pişkin,et al.  Functional copolymers of N-isopropylacrylamide for bioengineering applications , 2007 .

[141]  J. Burdick,et al.  Incorporation of Sulfated Hyaluronic Acid Macromers into Degradable Hydrogel Scaffolds for Sustained Molecule Delivery. , 2014, Biomaterials science.

[142]  Xian‐Zheng Zhang,et al.  Modular Synthesis of Thermosensitive P(NIPAAm-co-HEMA)/β-CD Based Hydrogels via Click Chemistry. , 2009, Macromolecular rapid communications.

[143]  J. Hubbell,et al.  Materials for Cell Encapsulation via a New Tandem Approach Combining Reverse Thermal Gelation and Covalent Crosslinking. , 2002 .

[144]  G. Prestwich Hyaluronic acid-based clinical biomaterials derived for cell and molecule delivery in regenerative medicine. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[145]  A. Lendlein,et al.  Shape-memory polymers , 2002 .

[146]  Kristi S. Anseth,et al.  A Versatile Synthetic Extracellular Matrix Mimic via Thiol‐Norbornene Photopolymerization , 2009, Advanced materials.

[147]  H. Klok,et al.  Synthese funktioneller Polymere durch polymeranaloge Reaktionen , 2009 .

[148]  Jennifer H Elisseeff,et al.  Modular Multifunctional Poly(ethylene glycol) Hydrogels for Stem Cell Differentiation , 2013, Advanced functional materials.

[149]  Marcia Simon,et al.  Hydrogels for Regenerative Medicine , 2016 .

[150]  Yan-Min Shen,et al.  Thermosensitive hydrogels synthesized by fast Diels–Alder reaction in water , 2009 .

[151]  V. Truong,et al.  Photodegradable Gelatin-Based Hydrogels Prepared by Bioorthogonal Click Chemistry for Cell Encapsulation and Release. , 2015, Biomacromolecules.

[152]  A. Mikos,et al.  Phosphorous-containing polymers for regenerative medicine , 2014, Biomedical materials.

[153]  Swati Pradhan-Bhatt,et al.  Hyaluronan: a simple polysaccharide with diverse biological functions. , 2014, Acta biomaterialia.

[154]  R. Reis,et al.  Biocompatibility Evaluation of Ionic‐ and Photo‐Crosslinked Methacrylated Gellan Gum Hydrogels: In Vitro and In Vivo Study , 2013, Advanced healthcare materials.

[155]  Ya Cao,et al.  Effects of Substitution Groups on the RAFT Polymerization of N-Alkylacrylamides in the Preparation of Thermosensitive Block Copolymers , 2007 .

[156]  J. Cui,et al.  Facile preparation of poly(N-isopropylacrylamide)-based hydrogels via aqueous Diels–Alder click reaction , 2010 .

[157]  T. Vermonden,et al.  Thermoresponsive Injectable Hydrogels Cross-Linked by Native Chemical Ligation , 2014 .

[158]  J. Hubbell,et al.  Towards a fully-synthetic substitute of alginate: development of a new process using thermal gelation and chemical cross-linking. , 2004, Biomaterials.

[159]  Thrimoorthy Potta,et al.  Injectable, dual cross-linkable polyphosphazene blend hydrogels. , 2010, Biomaterials.

[160]  Jason A. Burdick,et al.  Hyaluronic Acid Hydrogels for Biomedical Applications , 2011, Advanced materials.

[161]  B. Amsden,et al.  Methacrylated glycol chitosan as a photopolymerizable biomaterial. , 2007, Biomacromolecules.

[162]  Allan S Hoffman,et al.  Hydrogels for biomedical applications. , 2002, Advanced drug delivery reviews.

[163]  M. Gomes,et al.  Injectable gellan gum hydrogels with autologous cells for the treatment of rabbit articular cartilage defects , 2010, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[164]  T. Hoare,et al.  Designing injectable, covalently cross-linked hydrogels for biomedical applications. , 2014, Macromolecular rapid communications.

[165]  Kristi L. Kiick,et al.  Designing degradable hydrogels for orthogonal control of cell microenvironments , 2013, Chemical Society reviews.

[166]  R. Meyboom,et al.  Modulating rheological and degradation properties of temperature-responsive gelling systems composed of blends of PCLA-PEG-PCLA triblock copolymers and their fully hexanoyl-capped derivatives. , 2012, Acta biomaterialia.

[167]  Y. Zhu,et al.  Comb-shaped conjugates comprising hydroxypropyl cellulose backbones and low-molecular-weight poly(N-isopropylacryamide) side chains for smart hydrogels: synthesis, characterization, and biomedical applications. , 2010, Bioconjugate chemistry.

[168]  K. Park,et al.  Thermosensitive Chitosans as Novel Injectable Biomaterials , 2005 .

[169]  João Rodrigues,et al.  Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. , 2012, Chemical Society reviews.

[170]  E Ruoslahti,et al.  RGD and other recognition sequences for integrins. , 1996, Annual review of cell and developmental biology.

[171]  Takehisa Matsuda,et al.  Poly (N-isopropylacrylamide) (PNIPAM)-grafted gelatin as thermoresponsive three-dimensional artificial extracellular matrix: molecular and formulation parameters vs. cell proliferation potential , 2005, Journal of biomaterials science. Polymer edition.

[172]  B. Lee,et al.  Simultaneously physically and chemically gelling polymer system utilizing a poly(NIPAAm-co-cysteamine)-based copolymer. , 2007, Biomacromolecules.

[173]  J. Kopeček Hydrogel biomaterials: a smart future? , 2007, Biomaterials.

[174]  H. Kolmar,et al.  Correction: Combination of inverse electron-demand Diels-Alder reaction with highly efficient oxime ligation expands the toolbox of site-selective peptide conjugations. , 2015, Chemical communications.