Platelet-rich plasma gel promotes differentiation and regeneration during equine wound healing.

Carter, CA
·
Jolly, DG
·
Worden, CE
·
Hendren, DG
·
Kane, CJ

Abstract: Nonhealing wounds of the lower equine limb represent a challenging model. The platelet is a natural source of a myriad of growth factors and cytokines that promote wound healing. This study evaluates the potential of platelet derived factors to enhance wound healing in the lower equine limb. Platelets were isolated from horse blood and activated with thrombin, a process known to induce growth factor release. This produced a platelet gel composed of platelet-rich plasma (PRP). To test this all-natural wound healant, 2.5-cm(2) full thickness cutaneous wounds were created below the knee and hock of a thoroughbred horse. Wounds were treated with PRP gel or left untreated. Sequential wound biopsies collected at Days 7, 36, and 79 postwounding permitted comparison of the temporal expression of differentiation markers and wound repair. To test the hypothesis that wounds treated with PRP gel exhibit more rapid epithelial differentiation and enhanced organization of dermal collagen compared to controls, tissues were stained for cytokeratin 10, a suprabasal differentiation marker, and the reestablishment of collagen was evaluated by trichrome staining. PRP gel-treated wounds at Day 7 expressed intense cytokeratin 10 staining near the wound junction in suprabasal epidermal layers, while staining in control tissues was less intense and restricted to apical epidermal layers distal to the wound junction. By Day 79, the staining was equal in both groups. However, PRP gel-treated wounds at Day 79 contained abundant, dense collagen bundles oriented parallel to each other and to the overlying epithelium, whereas control tissues contained fewer collagen fibers that were oriented randomly. Thus, treatment of wounds with PRP gel induced accelerated epithelial differentiation and produced tissue with organized, interlocking collagen bundles. This study reveals that this novel all-natural wound healant induced wound repair in injuries previously deemed untreatable.

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Publication Date: 2003-06-05 PubMed ID: 12782011DOI: 10.1016/s0014-4800(03)00017-0Google Scholar: Lookup

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Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper looks at the deployment of platelet-rich plasma (PRP) gel in assisting the healing of wounds on horses’ lower limbs – wounds that are typically difficult to heal. Through controlled experimentation with PRP gel, the study shows that the treatment expedited epithelial differentiation and produced well-organized dermal collagen, resulting in enhanced wound healing.

Objective and Approach of the Research

The research primarily focuses on the potential of utilizing platelet-rich plasma (PRP) gel to significantly ameliorate the healing of non-healing equine lower limb wounds.
Platelets were obtained from horse blood and activated with thrombin, which led to the onset of growth factor release. This made a platelet gel composed of platelet-rich plasma (PRP).
For the experimental setup, full thickness cutaneous wounds of 2.5 cm² were formed below the knee and hock of a thoroughbred horse. These wounds were then treated with the developed PRP gel and some were left untreated for comparison.

Methodology and Observations

Biopsy samples were collected on the 7th, 36th, and 79th day post-wounding for comparing the expression of differentiation markers and the progression of wound repair.
This was performed to evaluate the hypothesis that PRP gel-treatment would lead to quicker epithelial differentiation and better organization of dermal collagen compared to the untreated wounds.
The researchers used staining methods to validate their hypothesis – cytokeratin 10 staining for examining the differentiation and trichrome staining for analyzing the collagen re-establishment.
On the 7th day, PRP gel-assisted wounds showed intense cytokeratin 10 staining near the wound junction in suprabasal epidermal layers, compared to a less intense staining in the untreated wounds.
On day 79, the staining was found to be homogeneous across both groups. However, the PRP-treated wounds showed a significant amount of well-organized, parallel-aligned collagen bundles, while the control group had lesser, randomly oriented collagen fibres.

Conclusion

The treatment of horse wounds with PRP gel facilitated an accelerated epithelial differentiation, and developed tissue complete with arranged, interlocking collagen bundles.
This research indicates that the novel all-natural wound treatment using PRP gel could be a significant solution in managing injuries previously considered non-treatable.

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APA

Carter CA, Jolly DG, Worden CE, Hendren DG, Kane CJ. (2003). Platelet-rich plasma gel promotes differentiation and regeneration during equine wound healing. Exp Mol Pathol, 74(3), 244-255. https://doi.org/10.1016/s0014-4800(03)00017-0

Publication

Experimental and molecular pathology

ISSN: 0014-4800

NlmUniqueID: 0370711

Country: Netherlands

Language: English

Volume: 74

Issue: 3

Pages: 244-255

Researcher Affiliations

Carter, Charleata A

Research Division, BeluMedX Equine Wound Healing, Little Rock, AR 72212, USA. charleatacarter@yahoo.com

Jolly, David G

Worden, Charles E

Hendren, Dennis G

Kane, Cynthia J M

MeSH Terms

Animals
Blood Platelets / drug effects
Blood Platelets / metabolism
Cell Differentiation
Collagen / metabolism
Enzyme-Linked Immunosorbent Assay
Gels / chemistry
Horse Diseases / drug therapy
Horse Diseases / pathology
Horse Diseases / physiopathology
Horses
Immunoenzyme Techniques
Keratin-10
Keratins / analysis
Keratins / metabolism
Male
Platelet-Derived Growth Factor / administration & dosage
Platelet-Derived Growth Factor / analysis
Platelet-Derived Growth Factor / metabolism
Regeneration
Skin / injuries
Skin / pathology
Thrombin / pharmacology
Transforming Growth Factor beta / analysis
Transforming Growth Factor beta / metabolism
Transforming Growth Factor beta1
Wound Healing / drug effects
Wound Healing / physiology

Citations

This article has been cited 50 times.

Iacopetti I, Perazzi A, Patruno M, Contiero B, Carolo A, Martinello T, Melotti L. Assessment of the quality of the healing process in experimentally induced skin lesions treated with autologous platelet concentrate associated or unassociated with allogeneic mesenchymal stem cells: preliminary results in a large animal model.. Front Vet Sci 2023;10:1219833.
doi: 10.3389/fvets.2023.1219833pubmed: 37559892google scholar: lookup
Troha K, Vozel D, Arko M, Bedina Zavec A, Dolinar D, Hou010devar M, Jan Z, Kisovec M, Kocjanu010diu010d B, Pau0111en L, Pajniu010d M, Peniu010d S, Romolo A, Repar N, Spasovski V, Steiner N, u0160uu0161tar V, Igliu010d A, Drobne D, Kogej K, Battelino S, Kralj-Igliu010d V. Autologous Platelet and Extracellular Vesicle-Rich Plasma as Therapeutic Fluid: A Review.. Int J Mol Sci 2023 Feb 8;24(4).
doi: 10.3390/ijms24043420pubmed: 36834843google scholar: lookup
Paulmann A, Strauss S, Limbourg A, Vogt PM. Platelet-derived concentrates influence human keratinocyte proliferation in vitro and induce wound healing in a prospective case series of chronic wounds of different entities in vivo.. Innov Surg Sci 2022 Jun;7(2):45-58.
doi: 10.1515/iss-2022-0011pubmed: 36317012google scholar: lookup
He M, Chen T, Lv Y, Song P, Deng B, Guo X, Rui S, Boey J, Armstrong DG, Ma Y, Deng W. The role of allogeneic platelet-rich plasma in patients with diabetic foot ulcer: Current perspectives and future challenges.. Front Bioeng Biotechnol 2022;10:993436.
doi: 10.3389/fbioe.2022.993436pubmed: 36246379google scholar: lookup
Verma R, Kumar S, Garg P, Verma YK. Platelet-rich plasma: a comparative and economical therapy for wound healing and tissue regeneration.. Cell Tissue Bank 2023 Jun;24(2):285-306.
doi: 10.1007/s10561-022-10039-zpubmed: 36222966google scholar: lookup
Kolimi P, Narala S, Nyavanandi D, Youssef AAA, Dudhipala N. Innovative Treatment Strategies to Accelerate Wound Healing: Trajectory and Recent Advancements.. Cells 2022 Aug 6;11(15).
doi: 10.3390/cells11152439pubmed: 35954282google scholar: lookup
Karina K, Ekaputri K, Biben JA, Hadi P, Andrew H, Sadikin PM. Therapeutic Effect of Autologous Activated Platelet-rich Plasma Therapy on Mid-dermal to Full-thickness Burns: A Case Series.. Arch Plast Surg 2022 May;49(3):405-412.
doi: 10.1055/s-0042-1744423pubmed: 35832167google scholar: lookup
Imam SS, Al-Abbasi FA, Hosawi S, Afzal M, Nadeem MS, Ghoneim MM, Alshehri S, Alzarea SI, Alquraini A, Gupta G, Kazmi I. Role of platelet rich plasma mediated repair and regeneration of cell in early stage of cardiac injury.. Regen Ther 2022 Mar;19:144-153.
doi: 10.1016/j.reth.2022.01.006pubmed: 35229012google scholar: lookup
Kim EY, Kim HS, Hong KS, Chung HM, Park SP, Noh G. Mesenchymal stem/stromal cell therapy in atopic dermatitis and chronic urticaria: immunological and clinical viewpoints.. Stem Cell Res Ther 2021 Oct 11;12(1):539.
doi: 10.1186/s13287-021-02583-4pubmed: 34635172google scholar: lookup
Nolan GS, Smith OJ, Heavey S, Jell G, Mosahebi A. Histological analysis of fat grafting with platelet-rich plasma for diabetic foot ulcers-A randomised controlled trial.. Int Wound J 2022 Feb;19(2):389-398.
doi: 10.1111/iwj.13640pubmed: 34169656google scholar: lookup
Camargo Garbin L, Lopez C, Carmona JU. A Critical Overview of the Use of Platelet-Rich Plasma in Equine Medicine Over the Last Decade.. Front Vet Sci 2021;8:641818.
doi: 10.3389/fvets.2021.641818pubmed: 33869321google scholar: lookup
Nolan GS, Smith OJ, Jell G, Mosahebi A. Fat grafting and platelet-rich plasma in wound healing: a review of histology from animal studies.. Adipocyte 2021 Dec;10(1):80-90.
doi: 10.1080/21623945.2021.1876374pubmed: 33525977google scholar: lookup
Iacopetti I, Patruno M, Melotti L, Martinello T, Bedin S, Badon T, Righetto EM, Perazzi A. Autologous Platelet-Rich Plasma Enhances the Healing of Large Cutaneous Wounds in Dogs.. Front Vet Sci 2020;7:575449.
doi: 10.3389/fvets.2020.575449pubmed: 33195571google scholar: lookup
Perinelli DR, Bonacucina G, Pucciarelli S, Cespi M, Serri E, Polzonetti V, Tambella AM, Vincenzetti S. Rheological Properties and Growth Factors Content of Platelet-Rich Plasma: Relevance in Veterinary Biomedical Treatments.. Biomedicines 2020 Oct 18;8(10).
doi: 10.3390/biomedicines8100429pubmed: 33081006google scholar: lookup
Chen D, Wang C, Cui L, Ran X. Autologous Platelet-Rich Gel Treatment of Chronic Nonhealing Ulcerated Tophaceous Gout.. Indian J Dermatol 2020 Mar-Apr;65(2):141-144.
doi: 10.4103/ijd.IJD_157_18pubmed: 32180603google scholar: lookup
Censi R, Casadidio C, Deng S, Gigliobianco MR, Sabbieti MG, Agas D, Laus F, Di Martino P. Interpenetrating Hydrogel Networks Enhance Mechanical Stability, Rheological Properties, Release Behavior and Adhesiveness of Platelet-Rich Plasma.. Int J Mol Sci 2020 Feb 19;21(4).
doi: 10.3390/ijms21041399pubmed: 32092976google scholar: lookup
Cortese L, Christopherson PW, Pelagalli A. Platelet Function and Therapeutic Applications in Dogs: Current Status and Future Prospects.. Animals (Basel) 2020 Jan 25;10(2).
doi: 10.3390/ani10020201pubmed: 31991713google scholar: lookup
Yim HE, Kim DS, Chung HC, Shing B, Moon KH, George SK, Kim MW, Atala Z, Kim JH, Ko IK, Yoo JJ. Controlled Delivery of Stem Cell-Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury in Rats.. Stem Cells Transl Med 2019 Sep;8(9):959-970.
doi: 10.1002/sctm.18-0222pubmed: 31144785google scholar: lookup
Mandla S, Davenport Huyer L, Radisic M. Review: Multimodal bioactive material approaches for wound healing.. APL Bioeng 2018 Jun;2(2):021503.
doi: 10.1063/1.5026773pubmed: 31069297google scholar: lookup
Rashed FM, GabAllah OM, AbuAli SY, Shredah MT. The Effect of Using Bone Marrow Mesenchymal Stem Cells Versus Platelet Rich Plasma on the Healing of Induced Oral Ulcer in Albino Rats.. Int J Stem Cells 2019 Mar 30;12(1):95-106.
doi: 10.15283/ijsc18074pubmed: 30836730google scholar: lookup
Chuncharunee A, Waikakul S, Wongkajornsilp A, Chongkolwatana V, Chuncharunee L, Sirimontaporn A, Rungruang T, Sreekanth GP. Invalid freeze-dried platelet gel promotes wound healing.. Saudi Pharm J 2019 Jan;27(1):33-40.
doi: 10.1016/j.jsps.2018.07.016pubmed: 30627050google scholar: lookup
Aydin O, Karaca G, Pehlivanli F, Altunkaya C, Uzun H, u00d6zden H, Aydin G, u015eahiner u0130T, Niyaz M, Gu00fcler O. Platelet-Rich Plasma May Offer a New Hope in Suppressed Wound Healing When Compared to Mesenchymal Stem Cells.. J Clin Med 2018 Jun 8;7(6).
doi: 10.3390/jcm7060143pubmed: 29890683google scholar: lookup
Chicharro-Alcu00e1ntara D, Rubio-Zaragoza M, Damiu00e1-Gimu00e9nez E, Carrillo-Poveda JM, Cuervo-Serrato B, Pelu00e1ez-Gorrea P, Sopena-Juncosa JJ. Platelet Rich Plasma: New Insights for Cutaneous Wound Healing Management.. J Funct Biomater 2018 Jan 18;9(1).
doi: 10.3390/jfb9010010pubmed: 29346333google scholar: lookup
Connolly D, Vu HL, Mariwalla K, Saedi N. Acne Scarring-Pathogenesis, Evaluation, and Treatment Options.. J Clin Aesthet Dermatol 2017 Sep;10(9):12-23.
pubmed: 29344322
Tambella AM, Attili AR, Dupru00e9 G, Cantalamessa A, Martin S, Cuteri V, Marcazzan S, Del Fabbro M. Platelet-rich plasma to treat experimentally-induced skin wounds in animals: A systematic review and meta-analysis.. PLoS One 2018;13(1):e0191093.
doi: 10.1371/journal.pone.0191093pubmed: 29324848google scholar: lookup
Park JW, Hwang SR, Yoon IS. Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration.. Molecules 2017 Jul 27;22(8).
doi: 10.3390/molecules22081259pubmed: 28749427google scholar: lookup
Shin HS, Woo HM, Kang BJ. Optimisation of a double-centrifugation method for preparation of canine platelet-rich plasma.. BMC Vet Res 2017 Jun 26;13(1):198.
doi: 10.1186/s12917-017-1123-3pubmed: 28651609google scholar: lookup
Abouelnasr K, Hamed M, Lashen S, El-Adl M, Eltaysh R, Tagawa M. Enhancement of abdominal wall defect repair using allogenic platelet-rich plasma with commercial polyester/cotton fabric (Damour) in a canine model.. J Vet Med Sci 2017 Jul 28;79(7):1301-1309.
doi: 10.1292/jvms.17-0139pubmed: 28603214google scholar: lookup
Salarinia R, Sadeghnia HR, Alamdari DH, Hoseini SJ, Mafinezhad A, Hosseini M. Platelet rich plasma: Effective treatment for repairing of spinal cord injury in rat.. Acta Orthop Traumatol Turc 2017 May;51(3):254-257.
doi: 10.1016/j.aott.2017.02.009pubmed: 28462801google scholar: lookup
Gemignani F, Perazzi A, Iacopetti I. Use of canine sourced platelet-rich plasma in a feline contaminated cutaneous wound.. Can Vet J 2017 Feb;58(2):141-144.
pubmed: 28216682
Pennicooke B, Moriguchi Y, Hussain I, Bonssar L, Hu00e4rtl R. Biological Treatment Approaches for Degenerative Disc Disease: A Review of Clinical Trials and Future Directions.. Cureus 2016 Nov 22;8(11):e892.
doi: 10.7759/cureus.892pubmed: 28018762google scholar: lookup
Yu00fcmu00fcn G, Kahaman C, Kahaman N, Yalu00e7u0131nkaya U, Aku00e7u0131lar A, Akgu00fcl E, Vural AH. Effects of hyperbaric oxygen therapy combined with platelet-rich plasma on diabetic wounds: an experimental rat model.. Arch Med Sci 2016 Dec 1;12(6):1370-1376.
doi: 10.5114/aoms.2016.62905pubmed: 27904531google scholar: lookup
Ostvar O, Shadvar S, Yahaghi E, Azma K, Fayyaz AF, Ahmadi K, Nowrouzian I. Retraction note: Effect of platelet-rich plasma on the healing of cutaneous defects exposed to acute to chronic wounds: a clinico-histopathologic study in rabbits.. Diagn Pathol 2016 Nov 2;11(1):113.
doi: 10.1186/s13000-016-0556-5pubmed: 27802803google scholar: lookup
Zhou J. A review of the application of autologous blood transfusion.. Braz J Med Biol Res 2016 Aug 1;49(9):e5493.
doi: 10.1590/1414-431X20165493pubmed: 27533770google scholar: lookup
Ozcelik U, Ekici Y, Bircan HY, Aydogan C, Turkoglu S, Ozen O, Moray G, Haberal M. Effect of Topical Platelet-Rich Plasma on Burn Healing After Partial-Thickness Burn Injury.. Med Sci Monit 2016 Jun 5;22:1903-9.
doi: 10.12659/msm.895395pubmed: 27262706google scholar: lookup
Jalowiec JM, D'Este M, Bara JJ, Denom J, Menzel U, Alini M, Verrier S, Herrmann M. An In Vitro Investigation of Platelet-Rich Plasma-Gel as a Cell and Growth Factor Delivery Vehicle for Tissue Engineering.. Tissue Eng Part C Methods 2016 Jan;22(1):49-58.
doi: 10.1089/ten.TEC.2015.0223pubmed: 26467221google scholar: lookup
Peru017eeu013eovu00e1 V, Sabol F, Vasilenko T, Novotnu00fd M, Kovu00e1u010d I, Slezu00e1k M, u010eurku00e1u010d J, Hollu00fd M, Pilu00e1tovu00e1 M, Szabo P, Varinsku00e1 L, u010criepokovu00e1 Z, Kuu010dera T, Kaltner H, Andru00e9 S, Gabius HJ, Muu010daji P, Smetana K Jr, Gu00e1l P. Pharmacological activation of estrogen receptors-u03b1 andu00a0-u03b2 differentially modulates keratinocyte differentiation with functional impact on wound healing.. Int J Mol Med 2016 Jan;37(1):21-8.
doi: 10.3892/ijmm.2015.2351pubmed: 26397183google scholar: lookup
Formica M, Cavagnaro L, Formica C, Mastrogiacomo M, Basso M, Di Martino A. What is the preclinical evidence on platelet rich plasma and intervertebral disc degeneration?. Eur Spine J 2015 Nov;24(11):2377-86.
doi: 10.1007/s00586-015-4189-2pubmed: 26272374google scholar: lookup
de Souza MV, Silva MB, Pinto Jde O, Lima MB, Crepaldi J, Lopes GF, dos Santos HB, Ribeiro RI, Thomu00e9 RG. Immunohistochemical Expression of Collagens in the Skin of Horses Treated with Leukocyte-Poor Platelet-Rich Plasma.. Biomed Res Int 2015;2015:893485.
doi: 10.1155/2015/893485pubmed: 26236743google scholar: lookup
Kuffler DP. Platelet-Rich Plasma Promotes Axon Regeneration, Wound Healing, and Pain Reduction: Fact or Fiction.. Mol Neurobiol 2015 Oct;52(2):990-1014.
doi: 10.1007/s12035-015-9251-xpubmed: 26048672google scholar: lookup
Chung TH, Baek DS, Kim N, Park JH, Park C. Topical allogeneic platelet-rich plasma treatment for a massive cutaneous lesion induced by disseminated intravascular coagulation in a toy breed dog.. Ir Vet J 2015;68(1):4.
doi: 10.1186/s13620-015-0032-7pubmed: 25763181google scholar: lookup
Lian Z, Yin X, Li H, Jia L, He X, Yan Y, Liu N, Wan K, Li X, Lin S. Synergistic effect of bone marrow-derived mesenchymal stem cells and platelet-rich plasma in streptozotocin-induced diabetic rats.. Ann Dermatol 2014 Feb;26(1):1-10.
doi: 10.5021/ad.2014.26.1.1pubmed: 24648680google scholar: lookup
Zhou B, Ren J, Ding C, Wu Y, Hu D, Gu G, Li J. Rapidly in situ forming platelet-rich plasma gel enhances angiogenic responses and augments early wound healing after open abdomen.. Gastroenterol Res Pract 2013;2013:926764.
doi: 10.1155/2013/926764pubmed: 24382956google scholar: lookup
Bernuzzi G, Petraglia F, Pedrini MF, De Filippo M, Pogliacomi F, Verdano MA, Costantino C. Use of platelet-rich plasma in the care of sports injuries: our experience with ultrasound-guided injection.. Blood Transfus 2014 Jan;12 Suppl 1(Suppl 1):s229-34.
doi: 10.2450/2013.0293-12pubmed: 23867186google scholar: lookup
Fontenot RL, Sink CA, Werre SR, Weinstein NM, Dahlgren LA. Simple tube centrifugation for processing platelet-rich plasma in the horse.. Can Vet J 2012 Dec;53(12):1266-72.
pubmed: 23729823
Guerid S, Darwiche SE, Berger MM, Applegate LA, Benathan M, Raffoul W. Autologous keratinocyte suspension in platelet concentrate accelerates and enhances wound healing - a prospective randomized clinical trial on skin graft donor sites: platelet concentrate and keratinocytes on donor sites.. Fibrogenesis Tissue Repair 2013 Apr 9;6(1):8.
doi: 10.1186/1755-1536-6-8pubmed: 23570605google scholar: lookup
Dionyssiou D, Demiri E, Foroglou P, Cheva A, Saratzis N, Aivazidis C, Karkavelas G. The effectiveness of intralesional injection of platelet-rich plasma in accelerating the healing of chronic ulcers: an experimental and clinical study.. Int Wound J 2013 Aug;10(4):397-406.
doi: 10.1111/j.1742-481X.2012.00996.xpubmed: 22672105google scholar: lookup
Su00e1nchez-Gonzu00e1lez DJ, Mu00e9ndez-Bolaina E, Trejo-Bahena NI. Platelet-rich plasma peptides: key for regeneration.. Int J Pept 2012;2012:532519.
doi: 10.1155/2012/532519pubmed: 22518192google scholar: lookup
Gu00e1l P, Vasilenko T, Kostelnu00edkovu00e1 M, Jakubco J, Kovu00e1c I, Sabol F, Andru00e9 S, Kaltner H, Gabius HJ, Smetana K Jr. Open Wound Healing In Vivo: Monitoring Binding and Presence of Adhesion/Growth-Regulatory Galectins in Rat Skin during the Course of Complete Re-Epithelialization.. Acta Histochem Cytochem 2011 Oct 26;44(5):191-9.
doi: 10.1267/ahc.11014pubmed: 22096259google scholar: lookup
Napolitano M, Matera S, Bossio M, Crescibene A, Costabile E, Almolla J, Almolla H, Togo F, Giannuzzi C, Guido G. Autologous platelet gel for tissue regeneration in degenerative disorders of the knee.. Blood Transfus 2012 Jan;10(1):72-7.
doi: 10.2450/2011.0026-11pubmed: 22044954google scholar: lookup