How Do Microneedle Patches Promote Burn Wound Repair through Sequential Delivery of Growth Factors?

I. What Key Challenges Does Burn Wound Repair Face?

Severe burn wounds are often accompanied by the destruction of key skin cell functions, leading to impaired re-epithelialization and delayed wound healing. The eschar formed at the burn site and the harsh microenvironment significantly hinder the effective delivery of therapeutic drugs, particularly impacting the delivery of growth factors. During wound repair, the activity of epithelial cells and fibroblasts is crucial for tissue regeneration; however, traditional drug delivery methods struggle to provide appropriate concentrations of growth factors at the precise times these cells need them most.

Keratinocyte Growth Factor-2, a member of the fibroblast growth factor family, specifically promotes epithelial cell proliferation and differentiation, while Acidic Fibroblast Growth Factor is a key regulator for the growth and differentiation of fibroblasts and endothelial cells. An ideal treatment strategy requires rapidly promoting epithelial regeneration in the early stages of wound healing, followed by sustained stimulation of dermal tissue repair. This sequential demand places higher requirements on drug delivery systems.

II. How Do Microneedle Patches Achieve Sequential Delivery of Growth Factors?

An innovative microneedle patch design employs a layered delivery strategy, successfully achieving the sequential release of two growth factors. By encapsulating Acidic Fibroblast Growth Factor in PLGA nanoparticles to form an NPaFGF complex, and then co-loading it with Keratinocyte Growth Factor-2 into the tip portion of the microneedle patch. This design utilizes methacrylated hyaluronic acid and riboflavin as matrix materials, fabricated via a photopolymerization process.

Release kinetics studies show that Keratinocyte Growth Factor-2, directly loaded into the microneedle matrix, releases rapidly—approximately 40% within the first four hours, reaching 90% cumulative release by the sixth day. This rapid release profile is beneficial for early promotion of epithelial cell proliferation and migration. In contrast, Acidic Fibroblast Growth Factor, encapsulated in nanoparticles, exhibits a slow-release characteristic, releasing only 2.3% in the first four hours and reaching 66% cumulative release after eleven days, ensuring sustained promotion of dermal tissue repair.

III. How Do the Physical Properties of the Microneedle Patch Ensure Effective Drug Delivery?

The structural design of the microneedle patch fully considers skin penetration capability and drug delivery efficiency. The patch base height is approximately 269 micrometers, and the needle tip height reaches 766 micrometers, sufficient to penetrate the epidermis and superficial dermis, delivering growth factors directly to the wound bed. Mechanical performance tests indicate that a single microneedle can withstand at least 0.2 Newtons of pressure, exceeding the minimum pressure of 0.15 Newtons required for skin puncture, ensuring the patch does not break during application.

In vivo experiments confirm that the microneedle patch can successfully penetrate the eschar barrier of burn wounds, with an average insertion depth of 331 micrometers, effectively overcoming the limitation of traditional topical formulations in penetrating eschar. The conical structure and appropriate mechanical strength of the microneedles enable transdermal drug delivery without causing significant pain, creating a direct delivery channel for growth factors to the wound site.

IV. How Does the Sequential Delivery System Modulate the Wound Microenvironment?

The regulatory effect of the microneedle patch sequential delivery system on the wound microenvironment is reflected at multiple levels. Immunohistochemical analysis shows significant upregulation of Hypoxia-Inducible Factor-1α and Heat Shock Protein 90 expression in the treatment group; both factors play key roles in angiogenesis and tissue repair. Western blot results further confirm that the expression level of Vascular Endothelial Growth Factor in the sequential delivery group is significantly higher than in other groups.

Regarding angiogenesis, the sequential delivery group exhibits the strongest CD31 and α-SMA positive signals, indicating significant improvement in both the quantity and maturity of new blood vessels. Meanwhile, Masson's trichrome staining reveals denser and more orderly collagen fiber arrangement in the sequential delivery group, indicating higher quality extracellular matrix reconstruction. These changes at the molecular and cellular levels collectively promote the transformation of the wound microenvironment towards a reparative state.

V. What is the Clinical Translation Prospect of the Sequential Delivery Strategy?

The strategy of sequentially delivering growth factors via microneedle patches provides a new approach for burn wound treatment. Compared to traditional single growth factor therapy, this sequential delivery system, designed based on the biology of the wound healing process, better aligns with the natural routine of tissue repair. Microneedle technology overcomes the limitation of traditional formulations in penetrating eschar, improving drug bioavailability at the wound site.

From a clinical application perspective, this microneedle patch offers advantages of ease of use and high patient compliance, making it suitable for various healthcare settings. Future research could further optimize release kinetics, explore combination strategies involving more growth factors, and expand applications to other types of hard-to-heal wounds. With advancements in materials science and manufacturing processes, this sequential delivery strategy is expected to become an important technological platform in the field of wound repair.

VI. Which Companies Supply Keratinocyte Growth Factor-2?

Hangzhou Start Biotech Co., Ltd. has independently developed the "EGF Protein, Human" (Product Name: EGF Protein, Human, Product Code: UA040003). This is a recombinant protein product characterized by high biological activity, high purity, and excellent stability. Produced using a mammalian expression system for recombinant expression and prepared via advanced purification processes, it holds significant application value in cell proliferation and differentiation research, wound healing mechanism exploration, and drug development.

Core Product Advantages:

·       High Biological Activity and Purity: Validated by cell proliferation assays, this product efficiently activates the EGFR signaling pathway, demonstrating exceptional biological activity. Through a multi-step chromatographic purification process, the product purity is >98% as analyzed by HPLC, with endotoxin levels <1.0 EU/μg, ensuring accurate and reliable experimental data.

·       Excellent Stability and Consistency: Under stringent quality control standards, the product exhibits outstanding physicochemical stability, with minimal intra-batch and inter-batch variation, providing stable and reliable support for scientific research and industrial applications.

Suitable for Various Key Application Scenarios: This product is an ideal tool for the following research areas:

·       Cell Proliferation and Differentiation Research: For in vitro proliferation and differentiation studies of various cell types including epidermal cells and keratinocytes.

·       Wound Healing and Tissue Repair: For exploring the mechanism of action and application research of EGF in skin wound repair and ulcer healing processes.

·       Signaling Pathway Mechanism Exploration: For investigating the mechanisms of EGFR signal transduction pathways and related crosstalk.

·       Drug Screening and Evaluation: Serves as an active ingredient or tool molecule for culture medium additives promoting cell growth and for the screening and potency evaluation of related drugs.

Professional Technical Support: We provide detailed product technical documentation, including complete purity analysis reports, activity validation data, and professional application solutions, fully committed to assisting customers in accelerating research progress and product development.

Hangzhou Start Biotech Co., Ltd. is consistently dedicated to providing high-quality, high-value biological reagents and solutions for global innovative pharmaceutical companies and research institutions. For more details about the "EGF Protein, Human" (Product Code UA040003) or to request a sample test, please feel free to contact us.

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