Application of silk proteins spidroin, fibroin, and sericin-based cream for reparative skin regeneration in vivo

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Abstract

BACKGROUND: Impaired reparative regeneration leads to insufficient extracellular matrix formation and the development of chronic wounds, necessitating a personalized therapeutic approach. In modern regenerative medicine, biopolymers such as silk proteins serve as the basis for wound dressings and drug delivery systems due to their unique properties. The biocompatibility, modulation of intracellular signaling pathways, and antibacterial activity of spidroin (spider silk protein), fibroin, and sericin (silkworm silk proteins) suggest their potential for wound healing applications.

AIM: To evaluate the effects of a spidroin, fibroin, and sericin-based cream on skin regeneration in rats.

METHODS: The study included 30 male rats, in which full-thickness excisional skin defects (20 mm in diameter) were created on the back. The animals were divided into three groups: the experimental group, which received daily applications of the test cream, and two control groups—one treated with 5% dexpanthenol and the other left to undergo natural wound healing. Planimetric and histomorphometric analyses, along with clinical blood tests, were performed to assess reparative regeneration and systemic reactive changes.

RESULTS: The application of the test cream significantly accelerated wound healing, with complete skin restoration in the experimental group by day 14 compared to the untreated control group. Analysis of inflammatory activity showed moderate granulocytosis and signs of acute posthemorrhagic anemia without pronounced inflammatory alterations in blood parameters. Additionally, immune cell infiltration was lower in the experimental group than in the controls.

CONCLUSION: The combination of spider silk proteins (spidroin) and silkworm silk proteins (fibroin and sericin) enhances cell migration, proliferation, and differentiation, promotes extracellular matrix formation, and exerts anti-inflammatory effects without immunogenic properties. These findings support the potential clinical use of this silk protein-based formulation as a therapeutic agent for treating wounds with pathological regeneration.

About the authors

Irina Sorochanu

North-Western State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: opeairina@gmail.com
ORCID iD: 0000-0002-6909-8937
SPIN-code: 4072-3845
Russian Federation, 41 Kirochnaja st, 191015, Saint Petersburg

Kristina S. Blitzine

North-Western State Medical University named after I.I. Mechnikov

Email: kristina.blitsyn@gmail.com
ORCID iD: 0000-0002-2347-0123
SPIN-code: 8210-8836
Russian Federation, 41 Kirochnaja st, 191015, Saint Petersburg

Dauddin I. Daudi

Saint-Petersburg National Research University of Information Technologies, Mechanics and Optics; Silkins LLC

Email: d.daudi@patentcore.ru
ORCID iD: 0000-0003-2413-3695
SPIN-code: 2765-0230
Russian Federation, Saint Petersburg; Moscow

Nikita I. Zhemkov

North-Western State Medical University named after I.I. Mechnikov

Email: zhemkovni@gmail.com
ORCID iD: 0009-0003-2423-6544
SPIN-code: 3779-4360
Russian Federation, 41 Kirochnaja st, 191015, Saint Petersburg

Alina A. Pechenina

North-Western State Medical University named after I.I. Mechnikov

Email: alina.kyzminap@gmail.com
ORCID iD: 0009-0003-7964-1256
SPIN-code: 8920-9532
Russian Federation, 41 Kirochnaja st, 191015, Saint Petersburg

Maria A. Dmitrieva

Saint-Petersburg National Research University of Information Technologies, Mechanics and Optics; Silkins LLC

Email: m_dmitrieva@scamt-itmo.ru
ORCID iD: 0009-0006-1596-3899
Russian Federation, Saint Petersburg; Moscow

Nikita A. Grin

Silkins LLC; Stavropol State Medical University

Email: nikita.grin.2014@mail.ru
ORCID iD: 0009-0000-4145-7160
SPIN-code: 5964-9291
Russian Federation, Moscow; Stavropol

Tatevik T. Asatryan

North-Western State Medical University named after I.I. Mechnikov

Email: Tatevik.asatryan@szgmu.ru
ORCID iD: 0000-0002-9146-3080
SPIN-code: 5587-1360

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, 41 Kirochnaja st, 191015, Saint Petersburg

Vladislav V. Tatarkin

North-Western State Medical University named after I.I. Mechnikov

Email: vladislav.tatarkin@szgmu.ru
ORCID iD: 0000-0002-9599-3935
SPIN-code: 5008-4677

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, 41 Kirochnaja st, 191015, Saint Petersburg

Evgeniy M. Trunin

North-Western State Medical University named after I.I. Mechnikov

Email: evgeniy.trunin@szgmu.ru
ORCID iD: 0000-0002-2452-0321
SPIN-code: 5903-0288

MD, Dr. Sci. (Medicine), Professor

Russian Federation, 41 Kirochnaja st, 191015, Saint Petersburg

Roman V. Deev

Petrovsky National Research Centre Of Surgery

Email: romdey@gmail.com
ORCID iD: 0000-0001-8389-3841
SPIN-code: 2957-1687

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. Wound closure assessment: the black dashed line represents the initial wound area (at day 0, S0), and the red dashed line indicates the wound area at the control time point (Sx). Wound closure was calculated as the ratio of the closed wound area to its initial area, expressed as a percentage.

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3. Fig. 2. Planimetric wound analysis: а, wound healing and epithelialization changes under the influence of the test cream, dexpanthenol, and natural healing (control) at different time points; b, wound closure changes (the graph presents median values, with a statistically significant difference between the experimental and control groups observed on day 7, p = 0.010).

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4. Fig. 3. Histological examination of regenerating tissue in rats from different groups: а, histotopograms of the damaged areas and surrounding healthy tissues, stained with hematoxylin and eosin, ×40 (#, granulation tissue; |, boundary between the wound defect and the keratinocyte proliferation zone with epithelial layer growth; ↑, restoration of skin appendages; *, complete wound closure); b, changes of linear defect size, determined as the distance between the boundaries of epithelial growth zones (data presented as Me [Q1; Q3], where Me is the median, Q1 is the first quartile, and Q3 is the third quartile); с, inflammatory response intensity assessment using a semi-quantitative 4-point scale (0 points, no inflammation; 1–4 points, wound infiltration by inflammatory cells covering <25%, 25–50%, 50–75%, and >75% of the area, respectively).

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5. Appendix 1. Changes of laboratory parameters in clinical blood tests of rats in different groups
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