27 results found
Contessi Negrini N, Sharpe P, Angelova Volponi A, et al., 2021, Tunable crosslinking and adhesion of gelatin hydrogels via bioorthogonal click chemistry, ACS Biomaterials Science and Engineering, Vol: 7, Pages: 4330-4346, ISSN: 2373-9878
Engineering cytocompatible hydrogels with tunable physico-mechanical properties as a biomimetic three-dimensional extracellular matrix (ECM) is fundamental to guide cell response and target tissue regeneration or development of in vitro models. Gelatin represents an optimal choice given its ECM biomimetic properties; however, gelatin cross-linking is required to ensure structural stability at physiological temperature (i.e., T > Tsol–gel gelatin). Here, we use a previously developed cross-linking reaction between tetrazine (Tz)- and norbornene (Nb) modified gelatin derivatives to prepare gelatin hydrogels and we demonstrate the possible tuning of their properties by varying their degree of modification (DOM) and the Tz/Nb ratio (R). The percentage DOM of the gelatin derivatives was tuned between 5 and 15%. Hydrogels prepared with higher DOM cross-linked faster (i.e., 10–20 min) compared to hydrogels prepared with lower DOM (i.e., 60–70 min). A higher DOM and equimolar Tz/Nb ratio R resulted in hydrogels with lower weight variation after immersion in PBS at 37 °C. The mechanical properties of the hydrogels were tuned by varying DOM and R by 1 order of magnitude, achieving elastic modulus E values ranging from 0.5 (low DOM and nonequimolar Tz/Nb ratio) to 5 kPa (high DOM and equimolar Tz/Nb ratio). Human dental pulp stem cells were embedded in the hydrogels and successfully 3D cultured in the hydrogels (percentage viable cells >85%). An increase in metabolic activity and a more elongated cell morphology was detected for cells cultured in hydrogels with lower mechanical properties (E < 1 kPa). Hydrogels prepared with an excess of Tz or Nb were successfully adhered and remained in contact during in vitro cultures, highlighting the potential use of these hydrogels as compartmentalized coculture systems. The successful tuning of the gelatin hydrogel properties here developed by controlling their bioorthogonal cross-linking is promising for t
Contessi Negrini N, Angelova Volponi A, Higgins CA, et al., 2021, Scaffold-based developmental tissue engineering strategies for ectodermal organ regeneration, Materials Today Bio, Vol: 10, Pages: 1-22, ISSN: 2590-0064
Tissue engineering (TE) is a multidisciplinary research field aiming at the regeneration, restoration, or replacement of damaged tissues and organs. Classical TE approaches combine scaffolds, cells and soluble factors to fabricate constructs mimicking the native tissue to be regenerated. However, to date, limited success in clinical translations has been achieved by classical TE approaches, because of the lack of satisfactory biomorphological and biofunctional features of the obtained constructs. Developmental TE has emerged as a novel TE paradigm to obtain tissues and organs with correct biomorphology and biofunctionality by mimicking the morphogenetic processes leading to the tissue/organ generation in the embryo. Ectodermal appendages, for instance, develop in vivo by sequential interactions between epithelium and mesenchyme, in a process known as secondary induction. A fine artificial replication of these complex interactions can potentially lead to the fabrication of the tissues/organs to be regenerated. Successful developmental TE applications have been reported, in vitro and in vivo, for ectodermal appendages such as teeth, hair follicles and glands. Developmental TE strategies require an accurate selection of cell sources, scaffolds and cell culture configurations to allow for the correct replication of the in vivo morphogenetic cues. Herein, we describe and discuss the emergence of this TE paradigm by reviewing the achievements obtained so far in developmental TE 3D scaffolds for teeth, hair follicles, and salivary and lacrimal glands, with particular focus on the selection of biomaterials and cell culture configurations.
Fernandez-Medina I, Celiz A, 2019, Acellular biomaterial strategies for endodontic regeneration, Biomaterials Science, Vol: 7, Pages: 506-519, ISSN: 2047-4830
Dental decay is treated by removing infected dental tissues such as dentine and restoring the tooth with a material. However, the vast majority of these materials have been designed to be mechanically robust and bioinert, whereas the potential regenerative properties of a biomaterial have not been considered. In endodontics for example, materials are used to seal the pulp cavity to avoid bacterial colonisation of the tooth and prevent further infection. While these treatments are effective in the short term, many of these materials have not been designed to interface with the pulp tissue in a biocompatible manner and are often cytotoxic. This can lead to less favourable long-term outcomes such as devitalisation of the tooth via root-canal therapy or extraction of the tooth. Clinical outcomes could be improved if regenerative approaches were followed whereby the biology of the tooth is engineered for repair and regeneration often with the support of a biomaterial. Within these, acellular or cell homing approaches are particularly interesting, as some regulatory hurdles associated with cellular therapies could be circumvented which may aid their clinical translation. In this review, we highlight progress in regenerative dentistry and focus on exciting developments using acellular biomaterials for regenerating dental tissues.
Vining KH, Scherba JC, Bever AM, et al., 2018, Synthetic light-curable polymeric materials provide a supportive niche for dental pulp stem cells, Advanced Materials, Vol: 30, ISSN: 0935-9648
Dental disease annually affects billions of patients, and while regenerative dentistry aims to heal dental tissue after injury, existing polymeric restorative materials, or fillings, do not directly participate in the healing process in a bioinstructive manner. There is a need for restorative materials that can support native functions of dental pulp stem cells (DPSCs), which are capable of regenerating dentin. A polymer microarray formed from commercially available monomers to rapidly identify materials that support DPSC adhesion is used. Based on these findings, thiol-ene chemistry is employed to achieve rapid light-curing and minimize residual monomer of the lead materials. Several triacrylate bulk polymers support DPSC adhesion, proliferation, and differentiation in vitro, and exhibit stiffness and tensile strength similar to existing dental materials. Conversely, materials composed of a trimethacrylate monomer or bisphenol A glycidyl methacrylate, which is a monomer standard in dental materials, do not support stem cell adhesion and negatively impact matrix and signaling pathways. Furthermore, thiol-ene polymerized triacrylates are used as permanent filling materials at the dentin-pulp interface in direct contact with irreversibly injured pulp tissue. These novel triacrylate-based biomaterials have potential to enable novel regenerative dental therapies in the clinic by both restoring teeth and providing a supportive niche for DPSCs.
Bauer A, Gu L, Kwee B, et al., 2017, Hydrogel substrate stress-relaxation regulates the spreading and proliferation of mouse myoblasts., Acta Biomaterialia, Vol: 62, Pages: 82-90, ISSN: 1742-7061
Mechanical properties of the extracellular microenvironment are known to alter cellular behavior, such as spreading, proliferation or differentiation. Previous studies have primarily focused on studying the effect of matrix stiffness on cells using hydrogel substrates that exhibit purely elastic behavior. However, these studies have neglected a key property exhibited by the extracellular matrix (ECM) and various tissues; viscoelasticity and subsequent stress-relaxation. As muscle exhibits viscoelasticity, stress-relaxation could regulate myoblast behavior such as spreading and proliferation, but this has not been previously studied. In order to test the impact of stress relaxation on myoblasts, we created a set of two-dimensional RGD-modified alginate hydrogel substrates with varying initial elastic moduli and rates of relaxation. The spreading of myoblasts cultured on soft stress-relaxing substrates was found to be greater than cells on purely elastic substrates of the same initial elastic modulus. Additionally, the proliferation of myoblasts was greater on hydrogels that exhibited stress-relaxation, as compared to cells on elastic hydrogels of the same modulus. These findings highlight stress-relaxation as an important mechanical property in the design of a biomaterial system for the culture of myoblasts. STATEMENT OF SIGNIFICANCE: This article investigates the effect of matrix stress-relaxation on spreading and proliferation of myoblasts by using tunable elastic and stress-relaxing alginate hydrogels substrates with different initial elastic moduli. Many past studies investigating the effect of mechanical properties on cell fate have neglected the viscoelastic behavior of extracellular matrices and various tissues and used hydrogels exhibiting purely elastic behavior. Muscle tissue is viscoelastic and exhibits stress-relaxation. Therefore, stress-relaxation could regulate myoblast behavior if it were to be incorporated into the design of hydrogel substrates. Alto
Adhesion to wet and dynamic surfaces, including biological tissues, is important in many fields but has proven to be extremely challenging. Existing adhesives are cytotoxic, adhere weakly to tissues, or cannot be used in wet environments. We report a bioinspired design for adhesives consisting of two layers: an adhesive surface and a dissipative matrix. The former adheres to the substrate by electrostatic interactions, covalent bonds, and physical interpenetration. The latter amplifies energy dissipation through hysteresis. The two layers synergistically lead to higher adhesion energies on wet surfaces as compared with those of existing adhesives. Adhesion occurs within minutes, independent of blood exposure and compatible with in vivo dynamic movements. This family of adhesives may be useful in many areas of application, including tissue adhesives, wound dressings, and tissue repair.
Alexander M, Denning C, Celiz A, et al., 2017, Cell culture substrate, US20170191026A1
Patel AK, Tibbitt MW, Celiz AD, et al., 2016, High throughput screening for discovery of materials that control stem cell fate, CURRENT OPINION IN SOLID STATE & MATERIALS SCIENCE, Vol: 20, Pages: 202-211, ISSN: 1359-0286
nsights into the complex stem cell niche have identified the cell–material interface to be a potent reg-ulator of stem cell fate via material properties such as chemistry, topography and stiffness. In light of this,materials scientists have the opportunity to develop bioactive materials for stem cell culture that elicitspecific cellular responses. To accelerate materials discovery, high throughput screening platforms havebeen designed which can rapidly evaluate combinatorial material libraries in two and three-dimensionalenvironments. In this review, we present screening platforms for the discovery of material properties thatinfluence stem cell behavior.
Amin YYI, Runager K, Simoes F, et al., 2016, Combinatorial Biomolecular Nanopatterning for High-Throughput Screening of Stem-Cell Behavior, ADVANCED MATERIALS, Vol: 28, Pages: 1472-1476, ISSN: 0935-9648
Patel AK, Celiz A, Rajamohan D, et al., 2015, Synthetic Substrates for Serum free Culture of Human Stem Cell Derived Cardiomyocytes with Improved Maturity and Toxicological Sensitivity Identified using Combinatorial Materials Microarrays, 4th TERMIS World Congress, Publisher: MARY ANN LIEBERT, INC, Pages: S251-S252, ISSN: 1937-3341
Celiz A, Smith J, Patel A, et al., 2015, Discovery of a Novel Polymer for Human Pluripotent Stem Cell Expansion and Multi-Lineage Differentiation, 4th TERMIS World Congress, Publisher: MARY ANN LIEBERT, INC, Pages: S270-S270, ISSN: 1937-3341
Celiz A, Smith J, Patel A, et al., 2015, Discovery of a novel polymer for human pluripotent stem cell expansion and multi-lineage differentiation, Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727
Patel AK, Celiz A, Rajamohan D, et al., 2015, Synthetic Substrates for Serum free Culture of Human Stem Cell Derived Cardiomyocytes with Improved Maturity and Toxicological Sensitivity Identified using Combinatorial Materials Microarrays, TERMIS AM
Celiz AD, Smith JGW, Patel AK, et al., 2015, Discovery of a novel polymer for human pluripotent stem cell expansion and multilineage differentiation, Advanced Materials, Vol: 27, Pages: 4006-4012, ISSN: 0935-9648
A scalable and cost-effective synthetic polymer substrate that supports robust expansion and subsequent multilineage differentiation of human pluripotent stem cells (hPSCs) with defined commercial media is presented. This substrate can be applied to common cultureware and used off-the-shelf after long-term storage. Expansion and differentiation of hPSCs are performed entirely on the polymeric surface, enabling the clinical potential of hPSC-derived cells to be realized.
Patel AK, Celiz AD, Rajamohan D, et al., 2015, A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays, Biomaterials, Vol: 61, Pages: 257-265, ISSN: 0142-9612
Cardiomyocytes from human stem cells have applications in regenerative medicine and can provide models for heart disease and toxicity screening. Soluble components of the culture system such as growth factors within serum and insoluble components such as the substrate on which cells adhere to are important variables controlling the biological activity of cells. Using a combinatorial materials approach we develop a synthetic, chemically defined cellular niche for the support of functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) in a serum-free fully defined culture system. Almost 700 polymers were synthesized and evaluated for their utility as growth substrates. From this group, 20 polymers were identified that supported cardiomyocyte adhesion and spreading. The most promising 3 polymers were scaled up for extended culture of hESC-CMs for 15 days and were characterized using patch clamp electrophysiology and myofibril analysis to find that functional and structural phenotype was maintained on these synthetic substrates without the need for coating with extracellular matrix protein. In addition, we found that hESC-CMs cultured on a co-polymer of isobornyl methacrylate and tert-butylamino-ethyl methacrylate exhibited significantly longer sarcomeres relative to gelatin control. The potential utility of increased structural integrity was demonstrated in an in vitro toxicity assay that found an increase in detection sensitivity of myofibril disruption by the anti-cancer drug doxorubicin at a concentration of 0.05 μM in cardiomyocytes cultured on the co-polymer compared to 0.5 μM on gelatin. The chemical moieties identified in this large-scale screen provide chemically defined conditions for the culture and manipulation of hESC-CMs, as well as a framework for the rational design of superior biomaterials.
Patel AK, Celiz A, Rajamohan D, et al., 2015, Identification of a defined synthetic substrate for cultureof human cardiomyocytes, In Vitro Toxicology Society Annual Meeting
Smith JGW, Celiz AD, Patel AK, et al., 2015, Scaling human pluripotent stem cell expansion and differentiation: are cell factories becoming a reality?, REGENERATIVE MEDICINE, Vol: 10, Pages: 925-930, ISSN: 1746-0751
Celiz AD, Smith JGW, Patel AK, et al., 2014, Chemically diverse polymer microarrays and high throughput surface characterisation: a method for discovery of materials for stem cell culture, BIOMATERIALS SCIENCE, Vol: 2, Pages: 1604-1611, ISSN: 2047-4830
Celiz AD, Harrington HC, Hook AL, 2014, High throughput assessment and chemometric analysis of the interaction of epithelial and fibroblast cells with a polymer library, APPLIED SURFACE SCIENCE, Vol: 313, Pages: 926-935, ISSN: 0169-4332
Rao W, Celiz AD, Scurr DJ, et al., 2013, Ambient DESI and LESA-MS Analysis of Proteins Adsorbed to a Biomaterial Surface Using In-Situ Surface Tryptic Digestion, JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, Vol: 24, Pages: 1927-1936, ISSN: 1044-0305
Celiz AD, Hook AL, Scurr DJ, et al., 2013, ToF-SIMS imaging of a polymer microarray prepared using ink-jet printing of acrylate monomers, 18th International Conferenceon Secondary Ion Mass Spectrometry (SIMS XVIII), Publisher: WILEY-BLACKWELL, Pages: 202-205, ISSN: 0142-2421
Celiz AD, Scherman OA, 2010, A Facile Route to Ureidopyrimidinone-Functionalized Polymers via RAFT, JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, Vol: 48, Pages: 5833-5841, ISSN: 0887-624X
Celiz AD, Lee T-C, Scherman OA, 2009, Polymer-Mediated Dispersion of Gold Nanoparticles: Using Supramolecular Moieties on the Periphery, ADVANCED MATERIALS, Vol: 21, Pages: 3937-+, ISSN: 0935-9648
Celiz AD, Scherman OA, 2008, Dynamic reversible supramolecular polymers bearing hydrogen bonding end groups, ISSN: 0032-3934
Celiz AD, Scherman OA, 2008, Controlled ring-opening polymerization initiated via self-complementary hydrogen-bonding units, MACROMOLECULES, Vol: 41, Pages: 4115-4119, ISSN: 0024-9297
Celiz AD, Scherman OA, 2008, POLY 505-Dynamic reversible supramolecular polymers bearing hydrogen bonding end groups, 235th American-Chemical-Society National Meeting, Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727
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