Genetically Encoded XTEN‐based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies
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2024
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| author | Jennifer I. Bennett Mary O'Kelly Boit Nicole E. Gregorio Fan Zhang Ryan D. Kibler Jack W. Hoye Olivia Prado Peter B. Rapp Charles E. Murry Kelly R. Stevens Cole A. DeForest |
| author_facet | Jennifer I. Bennett Mary O'Kelly Boit Nicole E. Gregorio Fan Zhang Ryan D. Kibler Jack W. Hoye Olivia Prado Peter B. Rapp Charles E. Murry Kelly R. Stevens Cole A. DeForest Jennifer I. Bennett Mary O'Kelly Boit Nicole E. Gregorio Fan Zhang Ryan D. Kibler Jack W. Hoye Olivia Prado Peter B. Rapp Charles E. Murry Kelly R. Stevens Cole A. DeForest |
| collection | Wiley Open Access |
| contents | Genetically Encoded XTEN‐based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies Jennifer I. Bennett Mary O'Kelly Boit Nicole E. Gregorio Fan Zhang Ryan D. Kibler Jack W. Hoye Olivia Prado Peter B. Rapp Charles E. Murry Kelly R. Stevens Cole A. DeForest Advanced Science AbstractWhile direct cell transplantation holds great promise in treating many debilitating diseases, poor cell survival and engraftment following injection have limited effective clinical translation. Though injectable biomaterials offer protection against membrane‐damaging extensional flow and supply a supportive 3D environment in vivo that ultimately improves cell retention and therapeutic costs, most are created from synthetic or naturally harvested polymers that are immunogenic and/or chemically ill‐defined. This work presents a shear‐thinning and self‐healing telechelic recombinant protein‐based hydrogel designed around XTEN – a well‐expressible, non‐immunogenic, and intrinsically disordered polypeptide previously evolved as a genetically encoded alternative to PEGylation to “eXTENd” the in vivo half‐life of fused protein therapeutics. By flanking XTEN with self‐associating coil domains derived from cartilage oligomeric matrix protein, single‐component physically crosslinked hydrogels exhibiting rapid shear thinning and self‐healing through homopentameric coiled‐coil bundling are formed. Individual and combined point mutations that variably stabilize coil association enables a straightforward method to genetically program material viscoelasticity and biodegradability. Finally, these materials protect and sustain viability of encapsulated human fibroblasts, hepatocytes, embryonic kidney (HEK), and embryonic stem‐cell‐derived cardiomyocytes (hESC‐CMs) through culture, injection, and transcutaneous implantation in mice. These injectable XTEN‐based hydrogels show promise for both in vitro cell culture and in vivo cell transplantation applications. 10.1002/advs.202301708 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/advs.202301708 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_advs_202301708 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Genetically Encoded XTEN‐based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies Jennifer I. Bennett Mary O'Kelly Boit Nicole E. Gregorio Fan Zhang Ryan D. Kibler Jack W. Hoye Olivia Prado Peter B. Rapp Charles E. Murry Kelly R. Stevens Cole A. DeForest Advanced Science Genetically Encoded XTEN‐based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies Jennifer I. Bennett Mary O'Kelly Boit Nicole E. Gregorio Fan Zhang Ryan D. Kibler Jack W. Hoye Olivia Prado Peter B. Rapp Charles E. Murry Kelly R. Stevens Cole A. DeForest Advanced Science AbstractWhile direct cell transplantation holds great promise in treating many debilitating diseases, poor cell survival and engraftment following injection have limited effective clinical translation. Though injectable biomaterials offer protection against membrane‐damaging extensional flow and supply a supportive 3D environment in vivo that ultimately improves cell retention and therapeutic costs, most are created from synthetic or naturally harvested polymers that are immunogenic and/or chemically ill‐defined. This work presents a shear‐thinning and self‐healing telechelic recombinant protein‐based hydrogel designed around XTEN – a well‐expressible, non‐immunogenic, and intrinsically disordered polypeptide previously evolved as a genetically encoded alternative to PEGylation to “eXTENd” the in vivo half‐life of fused protein therapeutics. By flanking XTEN with self‐associating coil domains derived from cartilage oligomeric matrix protein, single‐component physically crosslinked hydrogels exhibiting rapid shear thinning and self‐healing through homopentameric coiled‐coil bundling are formed. Individual and combined point mutations that variably stabilize coil association enables a straightforward method to genetically program material viscoelasticity and biodegradability. Finally, these materials protect and sustain viability of encapsulated human fibroblasts, hepatocytes, embryonic kidney (HEK), and embryonic stem‐cell‐derived cardiomyocytes (hESC‐CMs) through culture, injection, and transcutaneous implantation in mice. These injectable XTEN‐based hydrogels show promise for both in vitro cell culture and in vivo cell transplantation applications. 10.1002/advs.202301708 http://creativecommons.org/licenses/by/4.0/ |
| title | Genetically Encoded XTEN‐based Hydrogels with Tunable Viscoelasticity and Biodegradability for Injectable Cell Therapies |
| topic | Advanced Science |
| url | https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202301708 |