The DOI matches its Crossref record, with a small difference in title or year; 39 of the 40 references it cites were found in a registry or an index; none of the 48 sources its claims cite is checked for support yet.
A review of a bi-layered living cell treatment (Apligraf) in the treatment of venous leg ulcers and diabetic foot ulcers
Open accessAbstract
Apligraf (Organogenesis, Canton, MA) is a bi-layered bioengineered skin substitute and was the first engineered skin US Food and Drug Administration (FDA)-approved to promote the healing of ulcers that have failed standard wound care. Constructed by culturing human foreskin-derived neonatal fibroblasts in a bovine type I collagen matrix over which human foreskin-derived neonatal epidermal keratinocytes are then cultured and allowed to stratify, Apligraf provides both cells and matrix for the nonhealing wound. Its exact mechanism of action is not known, but it is known to produce cytokines and growth factors similar to healthy human skin. Initially approved by the FDA in 1998 for the treatment of venous ulcers greater than one-month duration that have not adequately responded to conventional therapy, Apligraf later received approval in 2000 for treatment of diabetic foot ulcers of greater than three weeks duration. Herein, we review the use of Apligraf in the treatment of chronic venous leg ulcers and diabetic foot ulcers. Our goal is to provide a working understanding of appropriate patient selection and proper use of the product for any physician treating this segment of the aging population.
Overview
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TL;DR
This narrative review summarizes the use of Apligraf, a bi-layered bioengineered skin substitute of neonatal fibroblasts in bovine type I collagen overlaid with neonatal keratinocytes, for chronic venous leg ulcers (VLU) and diabetic foot ulcers (DFU). It covers the product's history, composition, mechanism, patient selection, application technique, and economic impact, drawing mainly on the two pivotal FDA-approval trials.
Key findings
- In the VLU pivotal trial (293 outpatients), Apligraf plus compression achieved complete healing in 63% versus 49% with compression alone at 6 months, with median time to closure of 61 versus 181 days; benefit was greatest in larger (>10 cm²) and longer-duration (>6 months) ulcers.
- In the DFU pivotal trial (208 patients, 24 US centers), 56% of Apligraf-treated patients achieved complete healing at 12 weeks versus 38% of controls, with median closure of 65 versus 90 days and an odds ratio for complete healing of 2.14 (95% CI 1.23–3.74); osteomyelitis and lower limb amputations were less frequent in the Apligraf group.
- Apligraf is described as immunologically inert with no clinical or laboratory evidence of rejection, though its constituent cells are relatively short-lived (less than 4 weeks in most patients).
- The review reports lower ulcer-related medical costs and improved quality of life (mainly reduced wound pain) with Apligraf versus conventional care, and in one VLU study an average ulcer size decrease of 2.37 cm²/week versus a 0.72 cm²/week increase in controls.
Methods
- Design: narrative review of the literature on Apligraf for VLU and DFU, including its history, composition, mechanism of action, patient selection, proper application, and economic impact.
- Evidence base: primarily the two pivotal randomized controlled trials supporting FDA approval (Falanga et al 1998 for VLU; Veves et al 2001 for DFU), plus additional published studies and case reports of other wound applications.
- The review also synthesizes practical guidance on identifying nonhealing wounds, negative predictive markers, wound bed preparation, and application/dressing technique.
Limitations
- The paper does not state explicit limitations of its own review.
- Evident from the text: this is a narrative (non-systematic) review with no described search strategy or formal quality appraisal, and it relies heavily on the two pivotal trials and on secondary sources for economic and quality-of-life claims.
- The text itself notes that the exact mechanism of action of Apligraf is not known and that its cells do not persist indefinitely, which limits mechanistic conclusions.
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Claims the paper makes
0 Valid · 0 Not valid · 38 Not checked · 18 Own results and interpretations
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It has shown promise as an effective clinical treatment of chronic nonhealing wounds, such as VLU and DFU, and has been utilized in a variety of acute and chronic wounds to facilitate healing.”
§ A review of a bi-layered living cell treatment (Apligraf ®) in the treatment of venous leg ulcers and diabetic foot ulcers > History of Apligraf ®
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“It was found to decrease pain at the operative site compared with patients whose wounds were covered with polyurethane film (Muhart et al 1999).”
§ A review of a bi-layered living cell treatment (Apligraf ®) in the treatment of venous leg ulcers and diabetic foot ulcers > History of Apligraf ®
What the sources say
- Not checked yetcites Muhart et al 1999 source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A check of a cited source is scheduled, or we don’t hold its full text yet; the claim is checked once it runs.
In the paper
“Its exact mechanism of action is not known, but it is known to produce cytokines and growth factors similar to healthy human skin.”
§ A review of a bi-layered living cell treatment (Apligraf ®) in the treatment of venous leg ulcers and diabetic foot ulcers > Abstract
What the sources say
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A statement the paper makes itself — it cites no source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Constructed by culturing human foreskin-derived neonatal fibroblasts in a bovine type I collagen matrix over which human foreskin-derived neonatal epidermal keratinocytes are then cultured and allowed to stratify, Apligraf provides both cells and matrix for the nonhealing wound.”
§ A review of a bi-layered living cell treatment (Apligraf ®) in the treatment of venous leg ulcers and diabetic foot ulcers > Abstract
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Living skin equivalent was also compared with autograft or polyurethane film in acute partial thickness donor site wounds and was found to have no toxic effect or clinically apparent rejection.”
§ A review of a bi-layered living cell treatment (Apligraf ®) in the treatment of venous leg ulcers and diabetic foot ulcers > History of Apligraf ®
What the sources say
- Not checked yetcites Muhart et al 1999 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
27 more claims
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Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ A review of a bi-layered living cell treatment (Apligraf ®) in the treatment of venous leg ulcers and diabetic foot ulcers > History of Apligraf ®
“the treatment of epidermolysis bullosa, showing that Apligraf treated areas healed faster than the areas treated with conventional therapy (Falabella et al 1999; Streit et al 2001)”
§ A review of a bi-layered living cell treatment (Apligraf ®) in the treatment of venous leg ulcers and diabetic foot ulcers > References
“33. Streit M Bohlen LM Braathen LR 2001 Ulcerative sarcoidosis successfully treated with Apligraf Dermatology 202 367 70 11455163”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ A review of a bi-layered living cell treatment (Apligraf ®) in the treatment of venous leg ulcers and diabetic foot ulcers > History of Apligraf ®
“ulcerative sarcoidosis that was unresponsive to steroid treatment (Falabella et al 2000)”
§ A review of a bi-layered living cell treatment (Apligraf ®) in the treatment of venous leg ulcers and diabetic foot ulcers > References
“13. Falabella AF Valencia IC Eaglstein WH 2000 Tissue-engineered skin (Apligraf) in the healing of patients with epidermolysis bullosa wounds Arch Dermatol 136 1225 30 11030768”
Citations
Cites
Falanga, V. (1998) · Archives of Dermatology · doi:10.1001/archderm.134.3.293 · Cited by 656
Veves, A., Falanga, V., Armstrong, D. G., Sabolinski, M. L., & Study, T. A. D. F. U. (2001) · Diabetes Care · doi:10.2337/diacare.24.2.290 · Cited by 643
Meerwaldt, R., Links, T. P., Graaff, R., Hoogenberg, K., Lefrandt, J. D., Baynes, J., Gans, R. O. B., & Smit, A. J. (2005) · Diabetologia · doi:10.1007/s00125-005-1828-x · Cited by 185
Healing of Diabetic Foot Ulcers and Pressure Ulcers With Human Skin Equivalent
Brem, H. (2000) · Archives of Surgery · doi:10.1001/archsurg.135.6.627 · Cited by 182
Tissue-Engineered Skin (Apligraf) in the Healing of Patients With Epidermolysis Bullosa Wounds
Falabella, A. F., Valencia, I. C., Eaglstein, W. H., & Schachner, L. A. (2000) · Archives of Dermatology · doi:10.1001/archderm.136.10.1225 · Cited by 173
A Composite Skin Substitute (Graftskin) for Surgical Wounds
Eaglstein, W. H., Iriondo, M., & LASZLO, K. S. (1995) · Dermatologic Surgery · doi:10.1111/j.1524-4725.1995.tb00709.x · Cited by 156
Protocol for the successful treatment of venous ulcers
Brem, H., Kirsner, R. S., & Falanga, V. (2004) · The American Journal of Surgery · doi:10.1016/s0002-9610(03)00284-8 · Cited by 156
Self-citationWaymack, P., Duff, R. G., & Sabolinski, M. (2000) · Burns · doi:10.1016/s0305-4179(00)00017-6 · Cited by 140
The diabetic foot: The importance of biofilms and wound bed preparation
Davis, S. C., Martinez, L. C., & Kirsner, R. S. (2006) · Current Diabetes Reports · doi:10.1007/s11892-006-0076-x · Cited by 137
Self-citationQuality of Life of Adults with Unhealed and Healed Diabetic Foot Ulcers
Goodridge, D. M., Trepman, E., Sloan, J. A., Guse, L. W., Strain, L. A., McIntyre, J., & Embil, J. M. (2006) · Foot & Ankle International · doi:10.1177/107110070602700408 · Cited by 127
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Zeng, Q., Macri, L. K., Prasad, A., Clark, R. A. F., Zeugolis, D. I., Hanley, C., Garcia, Y., & Pandit, A. S. (2011) · Elsevier eBooks · doi:10.1016/b978-0-08-055294-1.00186-0 · Cited by 34
Yassaghi, Y., Nazerian, Y., Niazi, F., & Niknejad, H. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03901-2 · Cited by 32
Jahani, B., Wang, X., & Brooks, A. E. (2020) · Recent Progress in Materials · doi:10.21926/rpm.2003021 · Cited by 32
Chen, A., Huang, W., Wu, L. L., An, Y., Xuan, T., He, H., Ye, M., Qi, L., & Wu, J. (2020) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c00096 · Cited by 31
Monsuur, H. N., Weijers, E. M., Niessen, F. B., Gefen, A., Koolwijk, P., Gibbs, S., & van den Broek, L. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0167056 · Cited by 30
Ghosh, S., Haldar, S., Gupta, S., Chauhan, S., Mago, V., Roy, P., & Debrupa Lahiri, A. (2022) · Biomaterials Advances · doi:10.1016/j.bioadv.2022.212980 · Cited by 30
Nillesen, S. T. M., Lammers, G., Wismans, R. G., Ulrich, M. M. W., Middelkoop, E., Spauwen, P. H. M., Faraj, K. A., Schalkwijk, J., Daamen, W. F., & Kuppevelt, T. H. V. (2010) · Acta Biomaterialia · doi:10.1016/j.actbio.2010.10.011 · Cited by 30
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Waste-derived biomaterials as building blocks in the biomedical field
Jana, S., Das, P., Mukherjee, J., Banerjee, D. K., Ghosh, P. R., Das, P. K., Bhattacharya, R. N., & Nandi, S. K. (2021) · Journal of Materials Chemistry B · doi:10.1039/d1tb02125g · Cited by 27
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Tallapaneni, V., Kalaivani, C., Pamu, D., Mude, L., Singh, S. K., & Karri, V. V. S. R. (2021) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-021-00344-1 · Cited by 26
Yeoh, F. H., Lee, C. S., Kang, Y. B., Wong, S. F., & Cheng, S. F. (2018) · Journal of Applied Polymer Science · doi:10.1002/app.46861 · Cited by 26
Melt electrowritten poly-lactic acid /nanodiamond scaffolds towards wound-healing patches
Wu, X., Li, W., Herlah, L., Koch, M., Wang, H., Schirhagl, R., & Włodarczyk-Biegun, M. K. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101112 · Cited by 25
Blok, C. S., Vink, L., Boer, E. M. D., van Montfrans, C., van den Hoogenband, H. M., Mooij, M. C., Gauw, S. A., Vloemans, J. F. P. M., Bruynzeel, I., van Kraan, A., et al. (2013) · Wound Repair and Regeneration · doi:10.1111/wrr.12082 · Cited by 25
Burn Center Organization and Cellular Therapy Integration: Managing Risks and Costs
Chemali, M., Laurent, A. E., Scaletta, C., Waselle, L., Simon, J.-P., Michetti, M., Brunet, J.-F., Flahaut, M., Hirt‐Burri, N., Raffoul, W., et al. (2021) · Journal of Burn Care & Research · doi:10.1093/jbcr/irab080 · Cited by 25
Torregrossa, M., Kakpenova, A., Simon, J. C., & Franz, S. (2021) · Biological Chemistry · doi:10.1515/hsz-2021-0145 · Cited by 25
Laurent, A. E., Hirt‐Burri, N., Scaletta, C., Michetti, M., Roessingh, A. D. B., Raffoul, W., & Applegate, L. A. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.557758 · Cited by 23
Al-Dourobi, K., Laurent, A. E., Deghayli, L., Flahaut, M., Abdel-Sayed, P., Scaletta, C., Michetti, M., Waselle, L., Simon, J.-P., Ezzi, O. E., et al. (2021) · Pharmaceuticals · doi:10.3390/ph14030201 · Cited by 23
Bioengineered Alternative Tissues in Diabetic Wound Healing
Garwood, C. S., Steinberg, J. S., & Kim, P. J. (2014) · Clinics in Podiatric Medicine and Surgery · doi:10.1016/j.cpm.2014.09.004 · Cited by 23
Pharmaceutical perspectives of impaired wound healing in diabetic foot ulcer
Lau, H.-C., & Kim, A. (2016) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-016-0268-6 · Cited by 23
Ganesan, O., Kiwanuka, H., Hamaguchi, R., & Orgill, D. P. (2025) · Frontiers in Surgery · doi:10.3389/fsurg.2025.1504563 · Cited by 22
An In-Situ Forming Skin Substitute Improves Healing Outcome in a Hypertrophic Scar Model
Hartwell, R., Poormasjedi‐Meibod, M., Chavez-Munoz, C. I., Jalili, R. B., Hosseini‐Tabatabaei, A., & Ghahary, A. (2014) · Tissue Engineering Part A · doi:10.1089/ten.tea.2014.0271 · Cited by 22
Pratsinis, H., Armatas, A. A., Dimozi, A., Lefaki, M., Vassiliu, P., & Kletsas, D. (2013) · Wound Repair and Regeneration · doi:10.1111/wrr.12110 · Cited by 21
Innovative Strategies for Tissue Engineering
Carvalho, J. L., de Carvalho, P. H., Assis, D., & Goes, A. M. (2013) · InTech eBooks · doi:10.5772/53337 · Cited by 20
Concise Review: Epidermal Grafting: The Case for Pluripotent Stem Cells
Lemaître, G., Nissan, X., Baldeschi, C., & Peschanski, M. (2011) · Stem Cells · doi:10.1002/stem.636 · Cited by 19
Chronic Leg Ulcers: Are Tissue Engineering and Biomaterials Science the Solution?
Kyriakidis, C., Lali, F. V., Greco, K. V., & García‐Gareta, E. (2021) · Bioengineering · doi:10.3390/bioengineering8050062 · Cited by 18
Fang, Z. H., Zhu, T., Shen, W., Tang, Q. M., Chen, J., Yin, Z., Ji, J., Heng, B. C., Ouyang, H., & Chen, X. (2014) · Tissue Engineering Part A · doi:10.1089/ten.tea.2013.0296 · Cited by 18
Mulder, G., & Lee, D. K. (2009) · PubMed · Cited by 18
Richards, S. M., Keller, C. G., Kreutzer, R., Greiner, G., Ley, S., Doelemeyer, A., Dubost, V., Flandre, T., Kirkland, S. C., Carbone, W., et al. (2023) · International Wound Journal · doi:10.1111/iwj.14447 · Cited by 17
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Yadav, A. K., Ujjwal, R. R., Tripathi, S., & Krishna, S. T. V. S. (2021) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201022666210927103755 · Cited by 17
Regenerative Materials That Facilitate Wound Healing
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Cantu, D. A., & Kao, W. J. (2013) · Advanced Healthcare Materials · doi:10.1002/adhm.201300063 · Cited by 16
Nanotechnology in tissue engineering: expanding possibilities with nanoparticles
Sardari, S., Hheidari, A., Ghodousi, M., Rahi, A., & Pishbin, E. (2024) · Nanotechnology · doi:10.1088/1361-6528/ad5cfb · Cited by 16
Hartmann-Fritsch, F., Hosper, N. A., Luginbühl, J., Biedermann, T., Ernst Reichmann, A., & Meuli, M. (2012) · Pediatric Surgery International · doi:10.1007/s00383-012-3207-2 · Cited by 16
Junkins‐Hopkins, J. M. (2010) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2010.09.729 · Cited by 16
Physiology and Pathophysiology of Wound Healing in Diabetes
Stojadinović, O., Pastar, I., Gordon, K. A., & Tomic‐Canic, M. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-791-0_7 · Cited by 16
Mesenchymal stem cells in skin wound healing
Aydemir, I., Öztürk, Ş., Sönmez, P. K., & Tuğlu, M. İ. (2016) · Anatomy (International Journal of Experimental and Clinical Anatomy) · doi:10.2399/ana.16.043 · Cited by 15
Is the tissue-engineered intestine clinically viable?
Dunn, J. (2008) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep1151 · Cited by 15
Cell-Biomaterial constructs for wound healing and skin regeneration
Safina, I., Childress, L., Myneni, S. R., Vang, K. B., & Biris, A. S. (2022) · Drug Metabolism Reviews · doi:10.1080/03602532.2021.2025387 · Cited by 14
Wolcott, R. D., & Cox, S. B. (2013) · Journal of Wound Care · doi:10.12968/jowc.2013.22.sup1.s26 · Cited by 14
Riabinin, A. A., Pankratova, M., Rogovaya, O. S., Vorotelyak, E. A., Terskikh, V. V., & Vasiliev, A. V. (2024) · BioMed Research International · doi:10.1155/2024/9947692 · Cited by 13
A choline bio-ionic liquid-functionalized gelatin methacryloyl hydrogel for chronic wound healing
Banerjee, A., Jabbari, P., Martins‐Green, M. M., & Noshadi, I. (2025) · European Polymer Journal · doi:10.1016/j.eurpolymj.2025.113787 · Cited by 13
Nita, M., Pliszczyński, J., Kosieradzki, M., & Fiedor, P. S. (2021) · Dermatology and Therapy · doi:10.1007/s13555-021-00578-w · Cited by 13
More effective cell-based therapy through biofilm suppression
Wolcott, R. D., & Cox, S. B. (2013) · Journal of Wound Care · doi:10.12968/jowc.2013.22.1.26 · Cited by 13
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Wong, V., Wan, D. C., Gurtner, G. C., & Longaker, M. T. (2012) · World Journal of Surgery · doi:10.1007/s00268-012-1710-1 · Cited by 13
Mukharya, A., Pokale, R., Roy, A. A., Soman, S., Kulkarni, S., Madhusoodanan, G., Manikkath, J., Farhana, S. A., Pandey, A. P., & Mutalik, S. (2024) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2024.106590 · Cited by 12
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Domínguez-Saavedra, G., & Hernández-Galván, J. M. (2021) · Cirugía Plástica · doi:10.35366/103715 · Cited by 12
Gauglitz, G. G. (2013) · Springer eBooks · doi:10.1007/978-3-7091-1133-8_3 · Cited by 12
Ren, J., Chan, K. M., Lai, P. K. K., Lau, C. B., Huang, Y., Leung, P. C., Fung, K., Yu, W. F. X., & Cho, C. H. (2012) · Phytotherapy Research · doi:10.1002/ptr.4615 · Cited by 12
Boink, M. A., Roffel, S., Breetveld, M., Thon, M., Haasjes, M. S. P., Waaijman, T., Scheper, R. J., Blok, C. S., & Gibbs, S. (2017) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2438 · Cited by 12
“Tissues in a Dish”: A Review of Organoids in Plastic Surgery
Chinta, M. S., desJardins-Park, H. E., Wan, D. C., & Longaker, M. T. (2020) · Plastic & Reconstructive Surgery Global Open · doi:10.1097/gox.0000000000002787 · Cited by 12
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Auxenfans, C., Valencia, R. G., Abdel-Sayed, P., Alaminos, M., Brunet, J.-F. B., Campos, F., Chato‐Astrain, J., Carmona, G., Roessingh, A. D. B., Droz-Georget, S. L., et al. (2025) · European Burn Journal · doi:10.3390/ebj6020030 · Cited by 10
Chen, X. X., Laurent, A. E., Liao, Z., Jaccoud, S., Abdel-Sayed, P., Flahaut, M., Scaletta, C., Raffoul, W., Applegate, L. A., & Hirt‐Burri, N. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15092334 · Cited by 10
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Application and Assessment of Allogeneic Fibroblasts for Cell Therapy.
Kouhbananinejad, S. M., Armin, F., Dabiri, S., Derakhshani, A., Iranpour, M., & Farsinejad, A. (2018) · PubMed Central · Cited by 10
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Diabetic foot syndrome--dermatological point of view.
Troskot, N., Duvančić, T., & Kolić, M. (2013) · PubMed · Cited by 7
Duchini, G., Itin, P. H., & Arnold, A. (2011) · Advances in Skin & Wound Care · doi:10.1097/01.asw.0000397898.56121.3f · Cited by 7
Mucosal Substitutes for Periodontal Soft Tissue Regeneration
Swati Gupta Pratibha, P. K. (2015) · Dentistry · doi:10.4172/2161-1122.1000327 · Cited by 7
Regenerative technologies in treatment of diabetic foot ulcers
Kalinin, R. E., Suchkov, I. A., MZHAVANADZE, N. D., Krylov, A. A., Isaev, A. A., Леонидович, П. И., & Deev, R. V. (2017) · Genes and Cells · doi:10.23868/gc120634 · Cited by 7
GLOBAL REGULATORY ASPECTS OF WOUND CARE AND BURN DRESSINGS
Yadav, V., Bansal, P., Mittal, A., & Singh, S. K. (2018) · Asian Journal of Pharmaceutical and Clinical Research · doi:10.22159/ajpcr.2018.v11i7.26772 · Cited by 7
Analysis of Cell-seeded, Collagen-rich Hydrogel for Wound Healing
Leon, D. S., Williams, T., Wang, Z., Leyden, J., Franklin, A., Kaizawa, Y., Chang, J., & Fox, P. M. (2020) · Plastic & Reconstructive Surgery Global Open · doi:10.1097/gox.0000000000003049 · Cited by 6
Development of Novel Microenvironments for Promoting Enhanced Wound Healing
Scull, G., & Brown, A. C. (2020) · Current Tissue Microenvironment Reports · doi:10.1007/s43152-020-00009-6 · Cited by 6
Avery, J. T., Qiao, J., Medeiros, E., Bollenbach, T. J., Kimmerling, K. A., & Mowry, K. C. (2022) · International Wound Journal · doi:10.1111/iwj.13889 · Cited by 6
Position Paper Progress in the development of biomimetic engineered human tissues
Cheema, U. (2023) · Journal of Tissue Engineering · doi:10.1177/20417314221145663 · Cited by 6
Cellular- and Acellular-Based Therapies: Skin Substitutes and Matrices
Cahn, B. A., & Lev‐Tov, H. A. (2020) · Updates in clinical dermatology · doi:10.1007/978-3-030-28872-3_15 · Cited by 6
Natural polymer based hydrogel systems for wound management
Chinta, M. L., Gandam, P. K., & Parcha, S. R. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90514-5.00006-7 · Cited by 6
Epidermal cells delivered for cutaneous wound healing
Hu, X., Yu, W., Sun, H., Wang, X., & Han, C. (2010) · Journal of Dermatological Treatment · doi:10.3109/09546634.2010.495741 · Cited by 6
Akter, F., Ibanez, J., & Bulstrode, N. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-805361-4.00003-5 · Cited by 6
Wound Care Center of Excellence: Guide to Operative Technique for Chronic Wounds
Howell, R. S., Gorenstein, S. A., Castellano, M., Slone, E., Woods, J. S., Gillette, B. M., Donovan, V., Criscitelli, T. M., Brem, H., & BRATHWAITE, C. E. M. (2017) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2017.11.002 · Cited by 6
Lamouty, M. A., Asl, N. S., Safari, A., Ebrahimi, M., & Daemi, H. (2023) · PubMed Central · doi:10.22074/cellj.2023.561869.1129 · Cited by 5
Tissue‐Engineered Human Skin Equivalents and Their Applications in Wound Healing
Yildirimer, L., Hobson, D., Lin, Z. Y., Cui, W., & Zhao, X. (2017) · Wiley eBooks · doi:10.1002/9783527689934.ch7 · Cited by 5
Wille, J. J., Burdge, J. J., & Park, J. Y. (2014) · Methods in molecular biology · doi:10.1007/7651_2014_72 · Cited by 5
Wound Dressings and Comparative Effectiveness Data
Sood, A. K., Kogan, S., & Granick, M. S. (2018) · Recent clinical techniques, results, and research in wounds · doi:10.1007/15695_2017_97 · Cited by 5
Role of Topical Biological Therapies and Dressings in Healing Ischemic Wounds
Orrapin, S., & Rekasem, K. (2018) · The International Journal of Lower Extremity Wounds · doi:10.1177/1534734618815360 · Cited by 5
A Narrative Review on Efficacy of Cell‐ and Tissue‐Based Therapies for Diabetic Foot Ulcer
Niroomand, B., Mohammadzadeh, I., Tabarzad, M., & Mohit, E. (2025) · Advanced Therapeutics · doi:10.1002/adtp.202400335 · Cited by 4
Leodoro, B., Chang, A., & Cama, J. K. (2014) · Journal of Pediatric Surgery Case Reports · doi:10.1016/j.epsc.2014.10.006 · Cited by 4
Tissue engineering in wound healing
Soriano-Ruiz, J. L., Ríos, M., López, E., Garrido, M. T., Clares, B., & Gálvez, P. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-90471-1.00017-7 · Cited by 4
Engineered Biomaterials for Chronic Wound Healing
Davenport, M., & Dickinson, L. E. (2018) · Recent clinical techniques, results, and research in wounds · doi:10.1007/15695_2017_92 · Cited by 4
Nanomaterials for Wound Healing
Uzunallı, G. (2019) · Stem cell biology and regenerative medicine · doi:10.1007/978-3-030-31202-2_3 · Cited by 4
A Pilot Trial Assessing the Feasibility and Efficacy of a Novel Powder for Rapid Wound Healing
Verly, M., Mason, E., Sheikh‐Oleslami, S., Jalili, R. B., Russ, B., Kilani, R. T., & Ghahary, A. (2021) · European Burn Journal · doi:10.3390/ebj2040018 · Cited by 4
Mucosal and gingival tissue engineering
Neiva, R., & Giannobile, W. V. (2011) · Elsevier eBooks · doi:10.1533/9780857092427.3.305 · Cited by 4
Use of Apligraf for a devascularized ulcer secondary to mastectomy and radiation
Vlassova, N., & Lazarus, G. S. (2011) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2011.05.042 · Cited by 4
Surgical Treatment in Acute Phase of Severe Burns - a Comprehensive Approach
Andrei, M.-C., Grosu-Bularda, A., Vermesan, O., Frunza, A., Popescu, Ș. A., Ionita, S., Teodoreanu, R. N., Al-Falah, K., Neagu, T. P., & Lascăr, I. (2018) · Medicina Moderna - Modern Medicine · doi:10.31689/rmm.2018.25.1.24 · Cited by 4
Keratin-Based Biotechnological Applications
Nayak, K. K., Parkhey, P., & Mazumdar, B. (2018) · Springer series on polymer and composite materials · doi:10.1007/978-3-030-02901-2_8 · Cited by 4
Engineering of Accepted Skin-Equivalent Tissue for Tissue Repair: Current State and Perspectives
Sharma, K. S., Ralston, D. R., Giblin, V., & MacNeil, S. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.65568-x · Cited by 4
Bucciarelli, A., & Motta, A. (2026) · Precision medicine and engineering. · doi:10.1016/j.preme.2026.100063 · Cited by 3
The Outlook for Novel Pharmaceutics
Parhizkar, M., & Tsaoulidis, D. A. (2022) · Future of business and finance · doi:10.1007/978-3-030-99838-7_16 · Cited by 3
Dias-Ferreira, J., Teixeira, M. C., Severino, P. B., Boonme, P., Jovanović, J., Zielińska, A., & Souto, E. B. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-90471-1.00020-7 · Cited by 3
Mulder, G., & Lee, D. K. (2009) · PubMed · Cited by 3
Persistence of bilayered living-cell therapy donor DNA 10 months after application: a case report.
Serena, T. E., & Bialas, P. (2009) · PubMed · Cited by 3
Elloso, M. S., & Gauglitz, G. G. (2020) · Springer eBooks · doi:10.1007/978-3-030-39193-5_6 · Cited by 3
Metadata
- Authors
- Zaulyanov, L., & Kirsner, R. S.
- Affiliations
- University of Miami (US)
- Corresponding author
- Zaulyanov, Larissa
- ORCID
- Kirsner, Robert S
- Venue
- Clinical Interventions in Aging
- Publisher
- Informa UK Limited
- Published
- 2007-03
- Volume
- 2
- Issue
- 1
- Pages
- 93-98
- ISSN
- 1176-9092 (ISSN-L)
- PMC
- PMC2684073
- OpenAlex
- W2067691626
- Cited by
- 266
- References
- 40
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 19 · 2023: 17 · 2022: 15 · 2021: 26 · 2020: 18 · 2019: 14 · 2018: 28 · 2017: 9 · 2016: 17 · 2015: 12 · 2014: 20 · 2013: 14 · 2012: 9
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Clinical Interventions in Aging (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Health Sciences › Medicine › Surgery › Diagnosis and Treatment of Venous Diseases
- Keywords
- Apligraf, bioengineered skin substitutes, venous leg ulcers, diabetic foot ulcer, chronic wounds, wound healing, human foreskin fibroblasts, keratinocytes, collagen matrix, cytokines and growth factors, patient selection
- MeSH terms
- Collagen, Humans, Varicose Ulcer, Foot Ulcer, Diabetic Foot, Patient Selection
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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