Imperial College London

DrAdamCeliz

Faculty of EngineeringDepartment of Bioengineering

Senior Lecturer
 
 
 
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Contact

 

a.celiz

 
 
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Location

 

3.19bSir Michael Uren HubWhite City Campus

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Summary

 

Publications

Publication Type
Year
to

33 results found

Ganabady K, Contessi Negrini N, Scherba JC, Nitschke BM, Alexander MR, Vining KH, Grunlan MA, Mooney DJ, Celiz ADet al., 2023, High-throughput screening of thiol-ene click chemistries for bone adhesive polymers, ACS Applied Materials and Interfaces, Vol: 15, Pages: 50908-50915, ISSN: 1944-8244

Metal surgical pins and screws are employed in millions of orthopedic surgical procedures every year worldwide, but their usability is limited in the case of complex, comminuted fractures or in surgeries on smaller bones. Therefore, replacing such implants with a bone adhesive material has long been considered an attractive option. However, synthesizing a biocompatible bone adhesive with a high bond strength that is simple to apply presents many challenges. To rapidly identify candidate polymers for a biocompatible bone adhesive, we employed a high-throughput screening strategy to assess human mesenchymal stromal cell (hMSC) adhesion toward a library of polymers synthesized via thiol-ene click chemistry. We chose thiol-ene click chemistry because multifunctional monomers can be rapidly cured via ultraviolet (UV) light while minimizing residual monomer, and it provides a scalable manufacturing process for candidate polymers identified from a high-throughput screen. This screening methodology identified a copolymer (1-S2-FT01) composed of the monomers 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATATO) and pentaerythritol tetrakis (3-mercaptopropionate) (PETMP), which supported highest hMSC adhesion across a library of 90 polymers. The identified copolymer (1-S2-FT01) exhibited favorable compressive and tensile properties compared to existing commercial bone adhesives and adhered to bone with adhesion strengths similar to commercially available bone glues such as Histoacryl. Furthermore, this cytocompatible polymer supported osteogenic differentiation of hMSCs and could adhere 3D porous polymer scaffolds to the bone tissue, making this polymer an ideal candidate as an alternative bone adhesive with broad utility in orthopedic surgery.

Journal article

Ganabady K, Celiz AD, 2023, Enzyme-Responsive Hydrogels As Skeletal Muscle Implants, European Chapter of the Tissue-Engineering-and-Regenerative-Medicine-International-Society (TERMIS), Publisher: MARY ANN LIEBERT, INC, ISSN: 1937-3341

Conference paper

Basalo AM, Konstantinidi R, Quinn SM, Patel AK, Celiz ADet al., 2023, Screening Poly(Beta-Amino Ester) Nanoparticles for mRNA Delivery to Primary Human Skin Cells for Lymphangiogenesis, European Chapter of the Tissue-Engineering-and-Regenerative-Medicine-International-Society (TERMIS), Publisher: MARY ANN LIEBERT, INC, ISSN: 1937-3341

Conference paper

Contessi N, Martino F, Hu Y, Kholia S, Pi P, Schiavello M, Emanueli C, Celiz ADet al., 2023, Protein-based hydrogel tissue adhesives for failing hearts, Publisher: MARY ANN LIEBERT, INC, ISSN: 1937-3341

Conference paper

Al Ansari DE, Hu Y, Negrini NC, Pirri D, Birdsey GM, Celiz ADet al., 2023, Three-dimensional <i>in vitro</i> spheroid-based lymphangiogenesis model using click-crosslinked gelatin hydrogels, Publisher: MARY ANN LIEBERT, INC, ISSN: 1937-3341

Conference paper

Caldeira J, Celiz A, Newell N, 2022, A biomechanical testing method to assess tissue adhesives for annulus closure, Journal of the Mechanical Behavior of Biomedical Materials, Vol: 129, Pages: 105150-105150, ISSN: 1751-6161

Intervertebral disc (IVD) degeneration has been linked to Low Back Pain (LBP) which affects over 80% of the population ranking first in terms of disability worldwide. Degeneration progresses with age and is often accompanied by annulus fibrosus (AF) tearing and nucleus pulposus (NP) herniation. Existing therapies fail to restore IVD function and may worsen AF defects, increasing the risk of reherniation in nearly 30% of patients. Current AF closure options are ineffective, presenting biological or mechanical limitations. Bioadhesives have potential use in this area, however methods to assess performance are limited. Herein, we propose a biomechanical testing method to assess bioadhesives’ capacity to seal AF tears.Two candidate bioadhesives to seal AF tears were evaluated; a tough hydrogel adhesive, and a cyanoacrylate-based glue. The adhesion energy at the interface between bovine discs and the tough hydrogel adhesive was quantified using a peel test (n=4). An experimental method to measure the burst pressure of IVDs was then developed. This method was used to quantify the burst pressure of intact (n=7), injured (AF punctured with a 21G needle; n=7), and sealed IVDs (after applying either the tough hydrogel adhesive patch as a sealant; n=5, or the cyanoacrylate-based glue over the AF tear; n=6).The tough adhesive yielded a strong adhesion energy of 239 ± 49 J/m2 during the peel tests. A maximum pressure of 13.2 ± 3.8 MPa was observed for intact discs in the burst pressure tests, which reduced by 61.4% to 5.1 ± 1.5 MPa in the injured IVDs (p < 0.01)). Application of a cyanoacrylate-based glue to injured IVDs did not recover the burst pressure with statistical significance, however, application of the tough adhesive to injured IVDs, restored burst pressure to 12.3 ± 4.5 MPa, which was not significantly different to the intact burst pressures.In this study, a simple biomechanical method to assess the performance of bioadhesives to

Journal article

Contessi Negrini N, Sharpe P, Angelova Volponi A, Celiz Aet 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

Journal article

Contessi Negrini N, Angelova Volponi A, Higgins CA, Sharpe PT, Celiz ADet 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.

Journal article

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.

Journal article

Vining KH, Scherba JC, Bever AM, Alexander MR, Celiz AD, Mooney DJet 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.

Journal article

Bauer A, Gu L, Kwee B, Li WA, Dellacherie M, Celiz AD, Mooney DJet 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

Journal article

Li J, Celiz AD, Yang J, Yang Q, Wamala I, Whyte W, Seo BR, Vasilyev NV, Vlassak JJ, Suo Z, Mooney DJet al., 2017, Tough adhesives for diverse wet surfaces, Science, Vol: 357, Pages: 378-381, ISSN: 0036-8075

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.

Journal article

Alexander M, Denning C, Celiz A, Smith J, Patel Aet al., 2017, Cell culture substrate, US20170191026A1

Patent

Patel AK, Tibbitt MW, Celiz AD, Davies MC, Langer R, Denning C, Alexander MR, Anderson DGet 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.

Journal article

Amin YYI, Runager K, Simoes F, Celiz A, Taresco V, Rossi R, Enghild JJ, Abildtrup LA, Kraft DCE, Sutherland DS, Alexander MR, Foss M, Ogaki Ret al., 2016, Combinatorial Biomolecular Nanopatterning for High-Throughput Screening of Stem-Cell Behavior, ADVANCED MATERIALS, Vol: 28, Pages: 1472-1476, ISSN: 0935-9648

Journal article

Celiz A, Smith J, Patel A, Hook A, Rajamohan D, George V, Patel M, Epa V, Singh T, Langer R, Anderson D, Allen N, Hay D, Winkler D, Barrett D, Davies M, Young L, Denning C, Alexander Met 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

Conference paper

Patel AK, Celiz A, Rajamohan D, Langer R, Anderson D, Davies M, Alexander M, Denning Cet 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

Conference paper

Celiz A, Smith J, Patel A, Hook A, Rajamohan D, George V, Patel M, Epa V, Singh T, Langer R, Anderson D, Allen N, Hay D, Winkler D, Barrett D, Davies M, Young L, Denning C, Alexander Met al., 2015, Discovery of a novel polymer for human pluripotent stem cell expansion and multi-lineage differentiation, Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727

Conference paper

Celiz AD, Smith JGW, Patel AK, Hook AL, Rajamohan D, George VT, Flatt L, Patel MJ, Epa VC, Singh T, Langer R, Anderson DG, Allen ND, Hay DC, Winkler DA, Barrett DA, Davies MC, Young LE, Denning C, Alexander MRet 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.

Journal article

Patel AK, Celiz AD, Rajamohan D, Anderson DG, Langer R, Davies MC, Alexander MR, Denning Cet 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.

Journal article

Patel AK, Celiz A, Rajamohan D, Alexander M, Denning Cet al., 2015, Identification of a defined synthetic substrate for cultureof human cardiomyocytes, In Vitro Toxicology Society Annual Meeting

Conference paper

Smith JGW, Celiz AD, Patel AK, Short RD, Alexander MR, Denning Cet 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

Journal article

Celiz AD, Smith JGW, Patel AK, Langer R, Anderson DG, Barrett DA, Young LE, Davies MC, Denning C, Alexander MRet 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

Journal article

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

Journal article

Celiz AD, Smith JGW, Langer R, Anderson DG, Winkler DA, Barrett DA, Davies MC, Young LE, Denning C, Alexander MRet al., 2014, Materials for stem cell factories of the future, NATURE MATERIALS, Vol: 13, Pages: 570-579, ISSN: 1476-1122

Journal article

Rao W, Celiz AD, Scurr DJ, Alexander MR, Barrett DAet 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

Journal article

Celiz AD, Hook AL, Scurr DJ, Anderson DG, Langer R, Davies MC, Alexander MRet 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

Conference paper

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

Journal article

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

Journal article

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