{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T04:06:11Z","timestamp":1794024371037,"version":"4.8.0"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000266","name":"RCUK | Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/T51780X\/1"],"award-info":[{"award-number":["EP\/T51780X\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"RCUK | Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/X52556X\/1"],"award-info":[{"award-number":["EP\/X52556X\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"RCUK | Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/T017929\/1"],"award-info":[{"award-number":["BB\/T017929\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X502959\/1"],"award-info":[{"award-number":["MR\/X502959\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","award":["IAA 2024\\3"],"award-info":[{"award-number":["IAA 2024\\3"]}],"id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000700","name":"Royal Commission for the Exhibition of 1851","doi-asserted-by":"publisher","award":["Industrial Fellowship"],"award-info":[{"award-number":["Industrial Fellowship"]}],"id":[{"id":"10.13039\/501100000700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["712949"],"award-info":[{"award-number":["712949"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"U.S. Department of Health Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["R01EB031032"],"award-info":[{"award-number":["R01EB031032"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"U.S. Department of Health Human Services | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM139768"],"award-info":[{"award-number":["P20GM139768"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat. Mater."],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Materials enabling the cell-responsive delivery of endogenous biologics, such as growth factors, have the potential to modulate wound repair cost-effectively and safely. Unlike passive drug delivery strategies that require supraphysiological doses of recombinant protein or stimuli-responsive systems that rely on external triggers, we demonstrate a strategy that harnesses cellular traction forces as an intrinsic delivery trigger. Traction-force-activated payloads are bioinspired aptamer constructs attached to biomaterial scaffolds that selectively harvest, concentrate and reactivate multiple endogenous growth factors from cells, injury sites and blood lysate in vivo (rat femur and mouse skin) and ex vivo (human skin), at doses orders of magnitude lower than current clinical standards. Unmodified oligonucleotide aptamers retain functionality in enzyme-rich wound environments, substantially expanding the translational potential of nucleic-acid-based therapeutics. The ability to harvest and redeliver endogenous growth factors without exogenous triggers, recombinant proteins or cold-chain logistics via mechanoresponsive biomaterials opens possibilities for accessible, cost-effective combinatorial biologic therapies.<\/jats:p>","DOI":"10.1038\/s41563-026-02682-8","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:02:16Z","timestamp":1785142936000},"page":"1646-1657","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Force-responsive biomaterials drive tissue repair by harnessing endogenous growth factors"],"prefix":"10.1038","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-0293","authenticated-orcid":false,"given":"Magdalene Y.","family":"Ho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6305-0801","authenticated-orcid":false,"given":"Nuria","family":"Oliva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Basu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2883-3971","authenticated-orcid":false,"given":"Marcos R.","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1864-5248","authenticated-orcid":false,"given":"Jose Antonio","family":"Duran-Mota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3767-9202","authenticated-orcid":false,"given":"Divya M.","family":"Gollapalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1027-1269","authenticated-orcid":false,"given":"Victor G.","family":"Szwarcberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Akhavani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6876-3608","authenticated-orcid":false,"given":"Kyle P.","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9718-777X","authenticated-orcid":false,"given":"Benjamin D.","family":"Almquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"2682_CR1","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1039\/C7BM00295E","volume":"5","author":"A Stejskalov\u00e1","year":"2017","unstructured":"Stejskalov\u00e1, A. & Almquist, B. D. Using biomaterials to rewire the process of wound repair. Biomater. Sci. 5, 1421\u20131434 (2017).","journal-title":"Biomater. Sci."},{"key":"2682_CR2","first-page":"3706315","volume":"2019","author":"L Ca\u00f1edo-Dorantes","year":"2019","unstructured":"Ca\u00f1edo-Dorantes, L. & Ca\u00f1edo-Ayala, M. Skin acute wound healing: a comprehensive review. Int. J. Inflam. 2019, 3706315 (2019).","journal-title":"Int. J. Inflam."},{"key":"2682_CR3","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.2337\/dc09-0651","volume":"32","author":"MM Iversen","year":"2009","unstructured":"Iversen, M. M. et al. History of foot ulcer increases mortality among individuals with diabetes: ten-year follow-up of the Nord-Tr\u00f8ndelag Health Study, Norway. Diabetes Care 32, 2193\u20132199 (2009).","journal-title":"Diabetes Care"},{"key":"2682_CR4","doi-asserted-by":"crossref","first-page":"e37","DOI":"10.1097\/BOT.0000000000000736","volume":"31","author":"MR Brinker","year":"2017","unstructured":"Brinker, M. R., Trivedi, A. & O\u2019Connor, D. P. Debilitating effects of femoral nonunion on health-related quality of life. J. Orthop. Trauma 31, e37\u2013e42 (2017).","journal-title":"J. Orthop. Trauma"},{"key":"2682_CR5","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.injury.2021.02.022","volume":"52","author":"AT Schade","year":"2021","unstructured":"Schade, A. T. et al. The economic burden of open tibia fractures: a systematic review. Injury 52, 1251\u20131259 (2021).","journal-title":"Injury"},{"key":"2682_CR6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1136\/bmjmilitary-2019-001375","volume":"166","author":"SK Stewart","year":"2020","unstructured":"Stewart, S. K., Tenenbaum, O., Higgins, C., Masouros, S. & Ramasamy, A. Fracture union rates across a century of war: a systematic review of the literature. BMJ Mil. Health 166, 271\u2013276 (2020).","journal-title":"BMJ Mil. Health"},{"key":"2682_CR7","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.1039\/D0BM00266F","volume":"8","author":"A Amirsadeghi","year":"2020","unstructured":"Amirsadeghi, A. et al. Vascularization strategies for skin tissue engineering. Biomater. Sci. 8, 4073\u20134094 (2020).","journal-title":"Biomater. Sci."},{"key":"2682_CR8","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1111\/iwj.12443","volume":"13","author":"CJ Phillips","year":"2016","unstructured":"Phillips, C. J. et al. Estimating the costs associated with the management of patients with chronic wounds using linked routine data. Int. Wound J. 13, 1193\u20131197 (2016).","journal-title":"Int. Wound J."},{"key":"2682_CR9","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/dme.13973","volume":"36","author":"M Kerr","year":"2019","unstructured":"Kerr, M. et al. The cost of diabetic foot ulcers and amputations to the National Health Service in England. Diabet. Med. 36, 995\u20131002 (2019).","journal-title":"Diabet. Med."},{"key":"2682_CR10","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.3390\/molecules22081259","volume":"22","author":"JW Park","year":"2017","unstructured":"Park, J. W., Hwang, S. R. & Yoon, I. S. Advanced growth factor delivery systems in wound management and skin regeneration. Molecules 22, 1259 (2017).","journal-title":"Molecules"},{"key":"2682_CR11","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1073\/pnas.90.4.1513","volume":"90","author":"ER Edelman","year":"1993","unstructured":"Edelman, E. R., Nugent, M. A. & Karnovsky, M. J. Perivascular and intravenous administration of basic fibroblast growth factor: vascular and solid organ deposition. Proc. Natl Acad. Sci. USA 90, 1513\u20131517 (1993).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2682_CR12","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1182\/blood.V64.2.458.458","volume":"64","author":"D Bowen-Pope","year":"1984","unstructured":"Bowen-Pope, D., Malpass, T., Foster, D. & Ross, R. Platelet-derived growth factor in vivo: levels, activity, and rate of clearance. Blood 64, 458\u2013469 (1984).","journal-title":"Blood"},{"key":"2682_CR13","doi-asserted-by":"crossref","first-page":"s41038\u2013019\u20130148","DOI":"10.1186\/s41038-019-0148-1","volume":"7","author":"S Yamakawa","year":"2019","unstructured":"Yamakawa, S. & Hayashida, K. Advances in surgical applications of growth factors for wound healing. Burns Trauma 7, s41038\u2013019\u20130148\u20131 (2019).","journal-title":"Burns Trauma"},{"key":"2682_CR14","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/ten.teb.2015.0357","volume":"22","author":"AW James","year":"2016","unstructured":"James, A. W. et al. A review of the clinical side effects of bone morphogenetic protein-2. Tissue Eng. Part B Rev. 22, 284\u2013297 (2016).","journal-title":"Tissue Eng. Part B Rev."},{"key":"2682_CR15","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4103\/2152-7806.76147","volume":"2","author":"N Epstein","year":"2011","unstructured":"Epstein, N. Pros, cons, and costs of INFUSE in spinal surgery. Surg. Neurol. Int. 2, 10 (2011).","journal-title":"Surg. Neurol. Int."},{"key":"2682_CR16","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1007\/s40264-014-0226-z","volume":"37","author":"BA Baldo","year":"2014","unstructured":"Baldo, B. A. Side effects of cytokines approved for therapy. Drug Saf. 37, 921\u2013943 (2014).","journal-title":"Drug Saf."},{"key":"2682_CR17","doi-asserted-by":"publisher","first-page":"455","DOI":"10.2165\/11534570-000000000-00000","volume":"33","author":"N Papanas","year":"2010","unstructured":"Papanas, N. & Maltezos, E. Benefit-risk assessment of becaplermin in the treatment of diabetic foot ulcers. Drug Saf. 33, 455\u2013461 (2010).","journal-title":"Drug Saf."},{"key":"2682_CR18","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.addr.2020.07.021","volume":"161\u2013162","author":"N Oliva","year":"2020","unstructured":"Oliva, N. & Almquist, B. D. Spatiotemporal delivery of bioactive molecules for wound healing using stimuli-responsive biomaterials. Adv. Drug Deliv. Rev. 161\u2013162, 22\u201341 (2020).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"2682_CR19","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1039\/C7MH00373K","volume":"4","author":"HW Ooi","year":"2017","unstructured":"Ooi, H. W., Hafeez, S., van Blitterswijk, C. A., Moroni, L. & Baker, M. B. Hydrogels that listen to cells: a review of cell-responsive strategies in biomaterial design for tissue regeneration. Mater. Horiz. 4, 1020\u20131040 (2017).","journal-title":"Mater. Horiz."},{"key":"2682_CR20","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/nrg1471","volume":"5","author":"H Kitano","year":"2004","unstructured":"Kitano, H. Biological robustness. Nat. Rev. Genet. 5, 826\u2013837 (2004).","journal-title":"Nat. Rev. Genet."},{"key":"2682_CR21","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1126\/science.1069981","volume":"295","author":"ME Csete","year":"2002","unstructured":"Csete, M. E. & Doyle, J. C. Reverse engineering of biological complexity. Science 295, 1664\u20131669 (2002).","journal-title":"Science"},{"key":"2682_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/srep20214","volume":"6","author":"L Cardelli","year":"2016","unstructured":"Cardelli, L., Csik\u00e1sz-Nagy, A., Dalchau, N., Tribastone, M. & Tschaikowski, M. Noise reduction in complex biological switches. Sci. Rep. 6, 20214 (2016).","journal-title":"Sci. Rep."},{"key":"2682_CR23","doi-asserted-by":"crossref","first-page":"6279","DOI":"10.1016\/j.biomaterials.2010.04.053","volume":"31","author":"FM Chen","year":"2010","unstructured":"Chen, F. M., Zhang, M. & Wu, Z. F. Toward delivery of multiple growth factors in tissue engineering. Biomaterials 31, 6279\u20136308 (2010).","journal-title":"Biomaterials"},{"key":"2682_CR24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3390\/jfb9010010","volume":"9","author":"D Chicharro-Alc\u00e1ntara","year":"2018","unstructured":"Chicharro-Alc\u00e1ntara, D. et al. Platelet rich plasma: new insights for cutaneous wound healing management. J. Funct. Biomater. 9, 10 (2018).","journal-title":"J. Funct. Biomater."},{"key":"2682_CR25","doi-asserted-by":"crossref","DOI":"10.1016\/j.cyto.2021.155560","volume":"144","author":"RG dos Santos","year":"2021","unstructured":"dos Santos, R. G. et al. The regenerative mechanisms of platelet-rich plasma: a review. Cytokine 144, 155560 (2021).","journal-title":"Cytokine"},{"key":"2682_CR26","doi-asserted-by":"crossref","first-page":"55659","DOI":"10.1021\/acsami.0c17142","volume":"12","author":"Z Qian","year":"2020","unstructured":"Qian, Z. et al. Improving chronic diabetic wound healing through an injectable and self-healing hydrogel with platelet-rich plasma release. ACS Appl. Mater. Interfaces 12, 55659\u201355674 (2020).","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"2682_CR27","doi-asserted-by":"crossref","first-page":"1806380","DOI":"10.1002\/adma.201806380","volume":"31","author":"A Stejskalov\u00e1","year":"2019","unstructured":"Stejskalov\u00e1, A., Oliva, N., England, F. J. & Almquist, B. D. Biologically inspired, cell-selective release of aptamer-trapped growth factors by traction forces. Adv. Mater. 31, 1806380 (2019).","journal-title":"Adv. Mater."},{"key":"2682_CR28","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1039\/D0MH01285H","volume":"7","author":"K Lei","year":"2020","unstructured":"Lei, K. & Tang, L. T cell force-responsive delivery of anticancer drugs using mesoporous silica microparticles. Mater. Horiz. 7, 3196\u20133200 (2020).","journal-title":"Mater. Horiz."},{"key":"2682_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-44061-w","volume":"15","author":"A Velusamy","year":"2024","unstructured":"Velusamy, A., Sharma, R., Rashid, S. A., Ogasawara, H. & Salaita, K. DNA mechanocapsules for programmable piconewton responsive drug delivery. Nat. Commun. 15, 704 (2024).","journal-title":"Nat. Commun."},{"key":"2682_CR30","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1054\/bjps.2002.3950","volume":"55","author":"OCS Cassell","year":"2002","unstructured":"Cassell, O. C. S., Hofer, S. O. P., Morrison, W. A. & Knight, K. R. Vascularisation of tissue-engineered grafts: the regulation of angiogenesis in reconstructive surgery and in disease states. Br. J. Plast. Surg. 55, 603\u2013610 (2002).","journal-title":"Br. J. Plast. Surg."},{"key":"2682_CR31","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1016\/j.biomaterials.2004.07.006","volume":"26","author":"RY Kannan","year":"2005","unstructured":"Kannan, R. Y., Salacinski, H. J., Sales, K., Butler, P. & Seifalian, A. M. The roles of tissue engineering and vascularisation in the development of micro-vascular networks: a review. Biomaterials 26, 1857\u20131875 (2005).","journal-title":"Biomaterials"},{"key":"2682_CR32","doi-asserted-by":"crossref","first-page":"tkaa022","DOI":"10.1093\/burnst\/tkaa022","volume":"8","author":"H Shahin","year":"2020","unstructured":"Shahin, H., Elmasry, M., Steinvall, I., S\u00f6berg, F. & El-Serafi, A. Vascularization is the next challenge for skin tissue engineering as a solution for burn management. Burns Trauma 8, tkaa022 (2020).","journal-title":"Burns Trauma"},{"key":"2682_CR33","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.tibtech.2016.03.002","volume":"34","author":"J Rouwkema","year":"2016","unstructured":"Rouwkema, J. & Khademhosseini, A. Vascularization and angiogenesis in tissue engineering: beyond creating static networks. Trends Biotechnol. 34, 733\u2013745 (2016).","journal-title":"Trends Biotechnol."},{"key":"2682_CR34","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1083\/jcb.200302047","volume":"161","author":"H Gerhardt","year":"2003","unstructured":"Gerhardt, H. et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J. Cell Biol. 161, 1163\u20131177 (2003).","journal-title":"J. Cell Biol."},{"key":"2682_CR35","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.12167","volume":"5","author":"B Ubezio","year":"2016","unstructured":"Ubezio, B. et al. Synchronization of endothelial Dll4-notch dynamics switch blood vessels from branching to expansion. eLife 5, e12167 (2016).","journal-title":"eLife"},{"key":"2682_CR36","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.17079","volume":"5","author":"EM Bridges","year":"2016","unstructured":"Bridges, E. M. & Harris, A. L. To branch or to expand?. eLife 5, e17079 (2016).","journal-title":"eLife"},{"key":"2682_CR37","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1172\/JCI18420","volume":"113","author":"CR Ozawa","year":"2004","unstructured":"Ozawa, C. R. et al. Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis. J. Clin. Invest. 113, 516\u2013527 (2004).","journal-title":"J. Clin. Invest."},{"key":"2682_CR38","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.1097\/01.LAB.0000107160.81875.33","volume":"83","author":"MN Nakatsu","year":"2003","unstructured":"Nakatsu, M. N. et al. VEGF121 and VEGF165 regulate blood vessel diameter through vascular endothelial growth factor receptor 2 in an in vitro angiogenesis model. Lab. Invest. 83, 1873\u20131885 (2003).","journal-title":"Lab. Invest."},{"key":"2682_CR39","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1096\/fj.06-6568fje","volume":"20","author":"G von Degenfeld","year":"2006","unstructured":"von Degenfeld, G. et al. Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia. FASEB J. 20, 2657\u20132659 (2006).","journal-title":"FASEB J."},{"key":"2682_CR40","doi-asserted-by":"crossref","first-page":"a006569","DOI":"10.1101\/cshperspect.a006569","volume":"3","author":"R Blanco","year":"2013","unstructured":"Blanco, R. & Gerhardt, H. VEGF and notch in tip and stalk cell selection. Cold Spring Harb. Perspect. Med. 3, a006569 (2013).","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"2682_CR41","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.mvr.2006.05.008","volume":"72","author":"P Parsons-Wingerter","year":"2006","unstructured":"Parsons-Wingerter, P. et al. A VEGF165-induced phenotypic switch from increased vessel density to increased vessel diameter and increased endothelial NOS activity. Microvasc. Res. 72, 91\u2013100 (2006).","journal-title":"Microvasc. Res."},{"key":"2682_CR42","first-page":"1006","volume":"161","author":"N LeBrasseur","year":"2003","unstructured":"LeBrasseur, N. Two ways VEGF-A builds a vessel. J. Cell Biol. 161, 1006 (2003).","journal-title":"J. Cell Biol."},{"key":"2682_CR43","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s00441-002-0605-0","volume":"309","author":"T Pufe","year":"2002","unstructured":"Pufe, T. et al. Quantitative measurement of the splice variants 120 and 164 of the angiogenic peptide vascular endothelial growth factor in the time flow of fracture healing: a study in the rat. Cell Tissue Res. 309, 387\u2013392 (2002).","journal-title":"Cell Tissue Res."},{"key":"2682_CR44","doi-asserted-by":"crossref","first-page":"722446","DOI":"10.3389\/fsurg.2021.722446","volume":"8","author":"A Sadeghifar","year":"2021","unstructured":"Sadeghifar, A. et al. The effect of waterpipe tobacco smoking on bone healing following femoral fractures in male rats. Front. Surg. 8, 722446 (2021).","journal-title":"Front. Surg."},{"key":"2682_CR45","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1007\/s10353-003-0012-0","volume":"35","author":"J Nanobashvili","year":"2003","unstructured":"Nanobashvili, J. et al. Comparison of angiogenic potential of human microvascular endothelial cells and human umbilical vein endothelial cells. Eur. Surg. 35, 214\u2013219 (2003).","journal-title":"Eur. Surg."},{"key":"2682_CR46","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/j.1365-2133.2009.09581.x","volume":"162","author":"T Makino","year":"2010","unstructured":"Makino, T. et al. Basic fibroblast growth factor stimulates the proliferation of human dermal fibroblasts via the ERK1\/2 and JNK pathways. Br. J. Dermatol. 162, 717\u2013723 (2010).","journal-title":"Br. J. Dermatol."},{"key":"2682_CR47","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/wrr.12205","volume":"22","author":"S Barrientos","year":"2014","unstructured":"Barrientos, S., Brem, H., Stojadinovic, O. & Tomic-Canic, M. Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen. 22, 569\u2013578 (2014).","journal-title":"Wound Repair Regen."},{"key":"2682_CR48","doi-asserted-by":"crossref","first-page":"C695","DOI":"10.1152\/ajpcell.00322.2010","volume":"301","author":"Y Wang","year":"2011","unstructured":"Wang, Y. et al. Regulation of VEGF-induced endothelial cell migration by mitochondrial reactive oxygen species. Am. J. Physiol. Cell Physiol. 301, C695\u2013C704 (2011).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2682_CR49","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/nrm1261","volume":"4","author":"C Birchmeier","year":"2003","unstructured":"Birchmeier, C., Birchmeier, W., Gherardi, E. & Vande Woude, G. F. Met, metastasis, motility and more. Nat. Rev. Mol. Cell Biol. 4, 915\u2013925 (2003).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2682_CR50","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev-bioeng-071516-044730","volume":"25","author":"I Georgakoudi","year":"2023","unstructured":"Georgakoudi, I. & Quinn, K. P. Label-free optical metabolic imaging in cells and tissues. Annu. Rev. Biomed. Eng. 25, 413\u2013443 (2023).","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"2682_CR51","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1039\/D3CS00194F","volume":"53","author":"H Zhang","year":"2024","unstructured":"Zhang, H., Vandesompele, J., Braeckmans, K., De Smedt, S. C. & Remaut, K. Nucleic acid degradation as barrier to gene delivery: a guide to understand and overcome nuclease activity. Chem. Soc. Rev. 53, 317\u2013360 (2024).","journal-title":"Chem. Soc. Rev."},{"key":"2682_CR52","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.3390\/ijms18081683","volume":"18","author":"S Ni","year":"2017","unstructured":"Ni, S. et al. Chemical modifications of nucleic acid aptamers for therapeutic purposes. Int. J. Mol. Sci. 18, 1683 (2017).","journal-title":"Int. J. Mol. Sci."},{"key":"2682_CR53","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1524-475X.2009.00466.x","volume":"17","author":"GS Schultz","year":"2009","unstructured":"Schultz, G. S. & Wysocki, A. Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen. 17, 153\u2013162 (2009).","journal-title":"Wound Repair Regen."},{"key":"2682_CR54","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1038\/s41563-025-02212-y","volume":"24","author":"D Wu","year":"2025","unstructured":"Wu, D. et al. Bioinstructive scaffolds enhance stem cell engraftment for functional tissue regeneration. Nat. Mater. 24, 1364\u20131374 (2025).","journal-title":"Nat. Mater."},{"key":"2682_CR55","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41551-019-0469-1","volume":"4","author":"M Mochizuki","year":"2020","unstructured":"Mochizuki, M. et al. Growth factors with enhanced syndecan binding generate tonic signalling and promote tissue healing. Nat. Biomed. Eng. 4, 463\u2013475 (2020).","journal-title":"Nat. Biomed. Eng."},{"key":"2682_CR56","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1126\/science.1247663","volume":"343","author":"MM Martino","year":"2014","unstructured":"Martino, M. M. et al. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science 343, 885\u2013888 (2014).","journal-title":"Science"},{"key":"2682_CR57","unstructured":"US Food and Drug Administration. Potency Assurance for Cellular and Gene Therapy Products: Draft Guidance for Industry https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/potency-assurance-cellular-and-gene-therapy-products (US Food and Drug Administration, 2023)."},{"key":"2682_CR58","unstructured":"European Medicines Agency. Guideline on Human Cell-Based Medicinal Products. Report No. EMEA\/CHMP\/410869\/2006 (European Medicines Agency, 2008)."},{"key":"2682_CR59","unstructured":"European Medicines Agency. Guideline on Potency Testing of Cell Based Immunotherapy Medicinal Products for the Treatment of Cancer. Report No. EMA\/CHMP\/BWP\/271475\/2006 Rev. 1 (European Medicines Agency, 2016)."},{"key":"2682_CR60","doi-asserted-by":"crossref","first-page":"1190016","DOI":"10.3389\/fmed.2023.1190016","volume":"10","author":"P Salmikangas","year":"2023","unstructured":"Salmikangas, P., Carlsson, B., Klumb, C., Reimer, T. & Thirstrup, S. Potency testing of cell and gene therapy products. Front. Med. 10, 1190016 (2023).","journal-title":"Front. Med."},{"key":"2682_CR61","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06183-4","volume":"9","author":"SA Ferreira","year":"2018","unstructured":"Ferreira, S. A. et al. Bi-directional cell-pericellular matrix interactions direct stem cell fate. Nat. Commun. 9, 4049 (2018).","journal-title":"Nat. Commun."},{"key":"2682_CR62","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/s41563-019-0307-6","volume":"18","author":"C Loebel","year":"2019","unstructured":"Loebel, C., Mauck, R. L. & Burdick, J. A. Local nascent protein deposition and remodelling guide mesenchymal stromal cell mechanosensing and fate in three-dimensional hydrogels. Nat. Mater. 18, 883\u2013891 (2019).","journal-title":"Nat. Mater."},{"key":"2682_CR63","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s10895-016-2014-x","volume":"27","author":"JG Bruno","year":"2017","unstructured":"Bruno, J. G. Long shelf life of a lyophilized DNA aptamer beacon assay. J. Fluoresc. 27, 439\u2013441 (2017).","journal-title":"J. Fluoresc."},{"key":"2682_CR64","first-page":"46","volume":"11","author":"S Kedzierski","year":"2012","unstructured":"Kedzierski, S., Khoshnejad, M. & Caltagirone, G. T. Synthetic antibodies: the emerging field of aptamers. Bioprocess. J. 11, 46\u201349 (2012).","journal-title":"Bioprocess. J."},{"key":"2682_CR65","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.jid.2019.09.019","volume":"140","author":"H Topouzi","year":"2019","unstructured":"Topouzi, H., Boyle, C. J., Williams, G. & Higgins, C. A. Harnessing the secretome of hair follicle fibroblasts to accelerate ex vivo healing of human skin wounds. J. Invest. Dermatol. 140, 1075\u20131084.e11 (2019).","journal-title":"J. Invest. Dermatol."},{"key":"2682_CR66","doi-asserted-by":"publisher","unstructured":"Quantitative Optical Imaging Lab. kylepquinn\/3D-MPM-registration: v1.0 - Initial Release - code related to Jones et al., Communications Biology, 2018. Zenodo https:\/\/doi.org\/10.5281\/zenodo.20707807 (2026).","DOI":"10.5281\/zenodo.20707807"},{"key":"2682_CR67","doi-asserted-by":"publisher","unstructured":"Quantitative Optical Imaging Lab. kylepquinn\/autofluorescence-infiltration-nature-materials: v1.0 - Initial Release. Zenodo https:\/\/doi.org\/10.5281\/zenodo.20708392 (2026).","DOI":"10.5281\/zenodo.20708392"}],"container-title":["Nature Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41563-026-02682-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41563-026-02682-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41563-026-02682-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:02:43Z","timestamp":1787752963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41563-026-02682-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":67,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["2682"],"URL":"https:\/\/doi.org\/10.1038\/s41563-026-02682-8","relation":{},"ISSN":["1476-1122","1476-4660"],"issn-type":[{"value":"1476-1122","type":"print"},{"value":"1476-4660","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"assertion":[{"value":"16 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"B.D.A. is an inventor on USA patent US11058632B2 for the TrAP technology described in this manuscript. M.Y.H. and B.D.A. are founders of Traxion Biotech, a spin-out company based on the TrAP technology. The other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}