The Use of Activated Platelet Rich Plasma (PRP) in Human Autologous Fat Transfer

Lipofilling Clinical Trial

Official title:

The Use of Activated Platelet Rich Plasma (PRP) in Human Autologous Fat Transfer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01461785
• Other study ID #: JWJSLIPOFILLING
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 22, 2011
• Last updated: October 13, 2017
• Start date: April 2012
• Est. completion date: January 2015

Study information

• Verified date: July 2012
• Source: Bergman Clinics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this prospective, randomized clinical trial, lipofilling of the midface with Platelet Rich Plasma (PRP) is compared with lipofilling of the midface without PRP. The main objective of this study is to investigate the effect of the addition of PRP to the autologous fat transfer on local skin quality improvement, graft survival, and recovery after the procedure.

Description:

Soft tissue augmentation by the means of lipofilling is nowadays a frequently used technique in all forms of plastic surgery. In aesthetic facial surgery it has shown to increase the rejuvenating effect, in reconstructive surgery it has earned its place in the correction of soft tissue defects and athropy.

Post-operative loss of volume of the transplanted fat remains an uncertain factor in the procedure. In current literature, there are three main hypotheses on etiology of postoperative decrease in the graft volume; 1: the viability of the injected fat cells 2: impaired graft revascularization at the target site 3: the degree of fibrosis in the target area. Mentioned factors have limited the application of (large) volume lipotransfer.

Positive effects of lipofilling on skin quality have been reported. Coleman observed softening of wrinkles, decreasing pore size and pigmentation improvements on graft sites. Possible mechanisms of the claimed regenerative properties of the lipograft are explained by the high number of adipose derived stem cells. Although frequently described in literature, no objective results have been published to this date.

In this prospective study the investigators examine new methods in preventing postoperative volume loss by the addition of Platelet Rich Plasma (PRP), derived from the patients own blood, to the injected fat graft. The added PRP contains a wide range of growth factors for instance: Epidermal growth factor (EGF), Platelet derived growth factor (PDGF-AA), Transforming growth factor (TGF-B1, TGF-B2), Fibroblast growth factor (FGF) and Vascular endothelial growth factor (VEGF).

All previously mentioned factors have shown to play a key role in tissue regeneration after tissue damage. Especially VEGF is of great interest with the ability to promote neo-angiogenesis in the graft, and thus, in theory, reducing fat necrosis and seroma formation.

Current, scientifically validated, use of PRP include treatment of chronic and soft tissue ulcerations, applications in the periodontal and oral surgery, maxillofacial surgery, orthopaedic and trauma surgery, cosmetic and plastic surgery, spinal surgery, heart bypass surgery, and burns. In all mentioned applications, PRP showed to have a positive influence on the tissue recovery and regeneration. Local PRP application in damaged animal and human skin showed to have regenerative properties. Structural changes to the dermal layer were observed in biopsies.

In this prospective, randomized clinical trial, lipofilling of the midface with PRP is compared with lipofilling of the midface without PRP. The main objective of this study is to investigate the effect of the addition of PRP to the autologous fat transfer on local skin quality improvement, graft survival, and recovery after the procedure.

The synergy achieved by lipofilling with PRP may hold many future applications in both reconstructive and aesthetic plastic surgery. Current limitation of lipofilling, especially large volume lipo transfer (allowing reconstruction in one procedure in stead of multiple with smaller volumes) and lipofilling in pour vascularised tissue (eg. fibrosis after radiation therapy) may be countered by the addition of PRP. Furthermore, the suggested local skin improvements could be used in scar revisions and burn treatment in the future, bypassing invasive surgery.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 30 Years to 65 Years

Eligibility

Inclusion Criteria:

• Females

• Aged 30-65

• Stable normal BMI (20-25) (1 year stable between 20-25)

Exclusion Criteria:

•• Male

• Aged below 30 or above 65 years

• Aged between 45 and 55 and in the menopause

• Aged between 55 and 65 and pre-menopause

• Prior operations in the mid-face

• Any oncological event in the patients history

• A known psychiatric condition

• A known systemic disease that will impair wound healing ( eg diabetus mellitus, known atherosclerosis with an event that required hospitalization, collagen diseases, diseases of the skin).

• Smoking

• 20<BMI<25 or an unstable BMI: 1 year plus-minus 5 points.

• Pregnancy or active child wish

• Frequent exposure to known carcinogenic substances ( eg. work related).

• Active or previous use of hormone replacement therapy.

Related Conditions & MeSH terms

• Human Autologous Fat Transfer
• Lipofilling

Intervention

Biological:
• Addition of PRP ( platelet rich plasma) to the lipograft
27 ml blood will be drawn from the patient. The blood will be prepared according to the GPS System instructions (Biomet Biologics, LLC, Warsaw, Indiana USA). This desktop-size centrifuge has disposable cylinders to separate the different blood components (platelet rich plasma, PRP, platelet poor plasma, PPP, and red blood cells). The PRP is activated by adding calcium (15-volume % Ca2+ Sandoz®). creating activated Platelet Rich Plasma (aPRP). The lipograft of Group A will be enriched with 3ml of autologous PRP

Procedure:
• Lipofilling of the midface
The Coleman technique for fat harvesting and injection is employed but refined by utilizing a smaller, custom-made cannula for harvesting (inner diameter, 1.3 mm). The abdomen and upper legs are donor sites. Approximately two to three times more fat is harvested than the estimated amount required for the procedure. Fat is centrifuged for three minutes at the maximum speed of 3000 revolutions per minute after which the oil layer (top) and serum/infiltrate layer (bottom) are drained away, preserving the preadipocyte-rich pellet. Fat injection is performed in 1-mm aliquots with a short, curved Coleman cannula. Between 13 and 23 mL of fat is injected into the deep subcutaneous plane of each side of the face, except for the lower lid/tear trough region (where the injection is performed in the supraperiosteal/submuscular plane) and the temporal area (where the level of injection was above the superficial fascia of the temporal muscle).

Locations

Country	Name	City	State
Netherlands	Bergman Clinics	The Hague	Zuid-holland

Sponsors (2)

Lead Sponsor	Collaborator
Bergman Clinics	Zimmer Biomet

Country where clinical trial is conducted

Netherlands, 

References & Publications (56)

Bhanot S, Alex JC. Current applications of platelet gels in facial plastic surgery. Facial Plast Surg. 2002 Feb;18(1):27-33. Review. — View Citation

Brucker M, Sati S, Spangenberger A, Weinzweig J. Long-term fate of transplanted autologous fat in a novel rabbit facial model. Plast Reconstr Surg. 2008 Sep;122(3):749-54. doi: 10.1097/PRS.0b013e3181815a41. — View Citation

Clauser L, Polito J, Mandrioli S, Tieghi R, Denes SA, Galiè M. Structural fat grafting in complex reconstructive surgery. J Craniofac Surg. 2008 Jan;19(1):187-91. doi: 10.1097/scs.0b013e31815c94f5. Erratum in: J Craniofac Surg. 2008 May;19(3):871. — View Citation

Coleman SR. Facial recontouring with lipostructure. Clin Plast Surg. 1997 Apr;24(2):347-67. — View Citation

Coleman SR. Structural fat grafting: more than a permanent filler. Plast Reconstr Surg. 2006 Sep;118(3 Suppl):108S-120S. — View Citation

Condé-Green A, Baptista LS, de Amorin NF, de Oliveira ED, da Silva KR, Pedrosa Cda S, Borojevic R, Pitanguy I. Effects of centrifugation on cell composition and viability of aspirated adipose tissue processed for transplantation. Aesthet Surg J. 2010 Mar;30(2):249-55. doi: 10.1177/1090820X10369512. — View Citation

de Jonge S, de Vos RJ, Van Schie HT, Verhaar JA, Weir A, Tol JL. One-year follow-up of a randomised controlled trial on added splinting to eccentric exercises in chronic midportion Achilles tendinopathy. Br J Sports Med. 2010 Jul;44(9):673-7. doi: 10.1136/bjsm.2008.052142. Epub 2008 Oct 6. — View Citation

Dogramaci Y, Kalaci A, Savas N, Duman IG, Yanat AN. Treatment of lateral epicondilitis using three different local injection modalities: a randomized prospective clinical trial. Arch Orthop Trauma Surg. 2009 Oct;129(10):1409-14. doi: 10.1007/s00402-009-0832-x. Epub 2009 Feb 14. — View Citation

Donofrio LM. Panfacial volume restoration with fat. Dermatol Surg. 2005 Nov;31(11 Pt 2):1496-505. — View Citation

Draaijers LJ, Botman YA, Tempelman FR, Kreis RW, Middelkoop E, van Zuijlen PP. Skin elasticity meter or subjective evaluation in scars: a reliability assessment. Burns. 2004 Mar;30(2):109-14. — View Citation

Ducic Y, Pontius AT, Smith JE. Lipotransfer as an adjunct in head and neck reconstruction. Laryngoscope. 2003 Sep;113(9):1600-4. — View Citation

El-Sharkawy H, Kantarci A, Deady J, Hasturk H, Liu H, Alshahat M, Van Dyke TE. Platelet-rich plasma: growth factors and pro- and anti-inflammatory properties. J Periodontol. 2007 Apr;78(4):661-9. — View Citation

Engebretsen L, Steffen K, Alsousou J, Anitua E, Bachl N, Devilee R, Everts P, Hamilton B, Huard J, Jenoure P, Kelberine F, Kon E, Maffulli N, Matheson G, Mei-Dan O, Menetrey J, Philippon M, Randelli P, Schamasch P, Schwellnus M, Vernec A, Verrall G. IOC consensus paper on the use of platelet-rich plasma in sports medicine. Br J Sports Med. 2010 Dec;44(15):1072-81. doi: 10.1136/bjsm.2010.079822. — View Citation

Eppley BL, Pietrzak WS, Blanton M. Platelet-rich plasma: a review of biology and applications in plastic surgery. Plast Reconstr Surg. 2006 Nov;118(6):147e-159e. Review. — View Citation

Erdim M, Tezel E, Numanoglu A, Sav A. The effects of the size of liposuction cannula on adipocyte survival and the optimum temperature for fat graft storage: an experimental study. J Plast Reconstr Aesthet Surg. 2009 Sep;62(9):1210-4. doi: 10.1016/j.bjps.2008.03.016. Epub 2008 Jun 20. — View Citation

Eremia S, Newman N. Long-term follow-up after autologous fat grafting: analysis of results from 116 patients followed at least 12 months after receiving the last of a minimum of two treatments. Dermatol Surg. 2000 Dec;26(12):1150-8. — View Citation

Ersek RA. Transplantation of purified autologous fat: a 3-year follow-up is disappointing. Plast Reconstr Surg. 1991 Feb;87(2):219-27; discussion 228. — View Citation

Ezure T, Hosoi J, Amano S, Tsuchiya T. Sagging of the cheek is related to skin elasticity, fat mass and mimetic muscle function. Skin Res Technol. 2009 Aug;15(3):299-305. doi: 10.1111/j.1600-0846.2009.00364.x. — View Citation

Ferrara N, Gerber HP. The role of vascular endothelial growth factor in angiogenesis. Acta Haematol. 2001;106(4):148-56. Review. — View Citation

Gimble J, Guilak F. Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy. 2003;5(5):362-9. Review. — View Citation

Henderson JL, Cupp CL, Ross EV, Shick PC, Keefe MA, Wester DC, Hannon T, McConnell D. The effects of autologous platelet gel on wound healing. Ear Nose Throat J. 2003 Aug;82(8):598-602. — View Citation

Jackson IT, Simman R, Tholen R, DiNick VD. A successful long-term method of fat grafting: recontouring of a large subcutaneous postradiation thigh defect with autologous fat transplantation. Aesthetic Plast Surg. 2001 May-Jun;25(3):165-9. — View Citation

Kim JH, Jung M, Kim HS, Kim YM, Choi EH. Adipose-derived stem cells as a new therapeutic modality for ageing skin. Exp Dermatol. 2011 May;20(5):383-7. doi: 10.1111/j.1600-0625.2010.01221.x. Epub 2011 Feb 28. — View Citation

Krupski WC, Reilly LM, Perez S, Moss KM, Crombleholme PA, Rapp JH. A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report. J Vasc Surg. 1991 Oct;14(4):526-32; discussion 532-6. — View Citation

Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound healing. Yale J Biol Med. 2010 Mar;83(1):1-9. Review. — View Citation

Lindeboom JA, Mathura KR, Aartman IH, Kroon FH, Milstein DM, Ince C. Influence of the application of platelet-enriched plasma in oral mucosal wound healing. Clin Oral Implants Res. 2007 Feb;18(1):133-9. — View Citation

Little JW. Applications of the classic dermal fat graft in primary and secondary facial rejuvenation. Plast Reconstr Surg. 2002 Feb;109(2):788-804. — View Citation

Madonna R, Geng YJ, De Caterina R. Adipose tissue-derived stem cells: characterization and potential for cardiovascular repair. Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1723-9. doi: 10.1161/ATVBAHA.109.187179. Epub 2009 Jul 23. Review. — View Citation

Martínez-Zapata MJ, Martí-Carvajal A, Solà I, Bolibar I, Angel Expósito J, Rodriguez L, García J. Efficacy and safety of the use of autologous plasma rich in platelets for tissue regeneration: a systematic review. Transfusion. 2009 Jan;49(1):44-56. doi: 10.1111/j.1537-2995.2008.01945.x. Epub 2008 Oct 14. Review. — View Citation

Mishra A, Woodall J Jr, Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med. 2009 Jan;28(1):113-25. doi: 10.1016/j.csm.2008.08.007. Review. — View Citation

Nakamura S, Ishihara M, Takikawa M, Murakami K, Kishimoto S, Nakamura S, Yanagibayashi S, Kubo S, Yamamoto N, Kiyosawa T. Platelet-rich plasma (PRP) promotes survival of fat-grafts in rats. Ann Plast Surg. 2010 Jul;65(1):101-6. doi: 10.1097/SAP.0b013e3181b0273c. — View Citation

Nedelec B, Correa JA, Rachelska G, Armour A, LaSalle L. Quantitative measurement of hypertrophic scar: interrater reliability and concurrent validity. J Burn Care Res. 2008 May-Jun;29(3):501-11. doi: 10.1097/BCR.0b013e3181710881. — View Citation

Nguyen A, Pasyk KA, Bouvier TN, Hassett CA, Argenta LC. Comparative study of survival of autologous adipose tissue taken and transplanted by different techniques. Plast Reconstr Surg. 1990 Mar;85(3):378-86; discussion 387-9. — View Citation

Nikolidakis D, Jansen JA. The biology of platelet-rich plasma and its application in oral surgery: literature review. Tissue Eng Part B Rev. 2008 Sep;14(3):249-58. doi: 10.1089/ten.teb.2008.0062. Review. — View Citation

Nishimura T, Hashimoto H, Nakanishi I, Furukawa M. Microvascular angiogenesis and apoptosis in the survival of free fat grafts. Laryngoscope. 2000 Aug;110(8):1333-8. — View Citation

Ono S, Ogawa R, Hyakusoku H. Re: Use of Aquamid as a filler for facial rejuvenation in orientals. J Plast Reconstr Aesthet Surg 2009;62:1245-9. J Plast Reconstr Aesthet Surg. 2010 Jul;63(7):1227-8. doi: 10.1016/j.bjps.2009.12.008. Epub 2010 Jan 12. — View Citation

Pallua N, Wolter T, Markowicz M. Platelet-rich plasma in burns. Burns. 2010 Feb;36(1):4-8. doi: 10.1016/j.burns.2009.05.002. Epub 2009 Jun 21. Review. — View Citation

Peerbooms JC, Sluimer J, Bruijn DJ, Gosens T. Positive effect of an autologous platelet concentrate in lateral epicondylitis in a double-blind randomized controlled trial: platelet-rich plasma versus corticosteroid injection with a 1-year follow-up. Am J Sports Med. 2010 Feb;38(2):255-62. doi: 10.1177/0363546509355445. — View Citation

Pietrzak WS, Eppley BL. Platelet rich plasma: biology and new technology. J Craniofac Surg. 2005 Nov;16(6):1043-54. Review. — View Citation

Pusic AL, Klassen AF, Scott AM, Cano SJ. Discussion. The measure of face-lift patient satisfaction: the Owsley Facelift Satisfaction Survey with a long-term follow-up study. Plast Reconstr Surg. 2010 Jul;126(1):258-60. doi: 10.1097/PRS.0b013e3181dbba19. — View Citation

Redaelli A, Romano D, Marcianó A. Face and neck revitalization with platelet-rich plasma (PRP): clinical outcome in a series of 23 consecutively treated patients. J Drugs Dermatol. 2010 May;9(5):466-72. — View Citation

Ryu HS, Joo YH, Kim SO, Park KC, Youn SW. Influence of age and regional differences on skin elasticity as measured by the Cutometer. Skin Res Technol. 2008 Aug;14(3):354-8. doi: 10.1111/j.1600-0846.2008.00302.x. — View Citation

Salemi S, Rinaldi C, Manna F, Guarneri GF, Parodi PC. Reconstruction of lower leg skin ulcer with autologous adipose tissue and platelet-rich plasma. J Plast Reconstr Aesthet Surg. 2008 Dec;61(12):1565-7. doi: 10.1016/j.bjps.2008.04.048. Epub 2008 Aug 10. — View Citation

Shashikiran ND, Reddy VV, Yavagal CM, Zakirulla M. Applications of platelet-rich plasma (PRP) in contemporary pediatric dentistry. J Clin Pediatr Dent. 2006 Summer;30(4):283-6. — View Citation

Silva A, Sampaio R. Anatomic ACL reconstruction: does the platelet-rich plasma accelerate tendon healing? Knee Surg Sports Traumatol Arthrosc. 2009 Jun;17(6):676-82. doi: 10.1007/s00167-009-0762-8. Epub 2009 Mar 14. — View Citation

Sommer B, Sattler G. Current concepts of fat graft survival: histology of aspirated adipose tissue and review of the literature. Dermatol Surg. 2000 Dec;26(12):1159-66. Review. — View Citation

Strasser EJ. Application of an objective grading system for the evaluation of cosmetic surgical results. Plast Reconstr Surg. 2002 Apr 15;109(5):1733-40. — View Citation

Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, Fraser JK, Hedrick MH. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med. 2005 Sep;54(3):132-41. Review. — View Citation

Tischler M. Platelet rich plasma. The use of autologous growth factors to enhance bone and soft tissue grafts. N Y State Dent J. 2002 Mar;68(3):22-4. — View Citation

Tronnier H, Wiebusch M, Heinrich U. Change in skin physiological parameters in space--report on and results of the first study on man. Skin Pharmacol Physiol. 2008;21(5):283-92. doi: 10.1159/000148045. Epub 2008 Jul 28. — View Citation

Tzikas TL. Lipografting: autologous fat grafting for total facial rejuvenation. Facial Plast Surg. 2004 May;20(2):135-43. — View Citation

Wang-Saegusa A, Cugat R, Ares O, Seijas R, Cuscó X, Garcia-Balletbó M. Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life. Arch Orthop Trauma Surg. 2011 Mar;131(3):311-7. doi: 10.1007/s00402-010-1167-3. Epub 2010 Aug 17. — View Citation

Wrotniak M, Bielecki T, Gazdzik TS. Current opinion about using the platelet-rich gel in orthopaedics and trauma surgery. Ortop Traumatol Rehabil. 2007 May-Jun;9(3):227-38. Review. English, Polish. — View Citation

Yamaguchi M, Matsumoto F, Bujo H, Shibasaki M, Takahashi K, Yoshimoto S, Ichinose M, Saito Y. Revascularization determines volume retention and gene expression by fat grafts in mice. Exp Biol Med (Maywood). 2005 Nov;230(10):742-8. — View Citation

Yamaguchi R, Terashima H, Yoneyama S, Tadano S, Ohkohchi N. Effects of platelet-rich plasma on intestinal anastomotic healing in rats: PRP concentration is a key factor. J Surg Res. 2012 Apr;173(2):258-66. doi: 10.1016/j.jss.2010.10.001. Epub 2010 Nov 2. — View Citation

Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002 Dec;13(12):4279-95. — View Citation

* Note: There are 56 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cutometry	Postoperative skin quality measured with a Multi Probe Adapter system (Courage Khanza Colone Germany) containing several skin measurement probes (Maxameter mx18: Assessing melanin content and erythema level, Tewameter TM300: Skin barrier function and transepidermal waterloss, Cutometer MPA580: Mechanical parameters of the skin) on predetermined fixed positions in the face on predetermined times . (pre-operative, 1 week postoperative, 3 months post-operative and 1 year post-operative.)	1 year post-operative of the last included patient, estimate is 18 months
Secondary	Panel assessment	Standardized photos will be taken pre-, and post-operatively ( at 3 months and 1 year follow-up ) The photos will be analysed by two separate panels using validated scoring systems ( an adapted Moolenburg and Strasser). Both questionnaires will focus on changes in facial volume. The panels will consist of five independent plastic surgeons and five laypersons (all blinded).(pre-operative, 3 months post-operative and 1 year post-operative.)	1 year post-operative of the last included patient, estimate is 18 months
Secondary	Patient questionnaire	Analysis of a patient questionnaire sent at 4 weeks post-operative, with number of complications, recovery time (return to work/ return to social activity) and patient self-assessment (visual analogue score) as main endpoints. This questionnaire will use the standardized FACE-Q list that will be published in the fourth quarter of 2011. Use of topical skin products and sun exposure will be added to this questionnaire.	1 year post-operative of the last included patient, estimate is 18 months