Plant-Based Bioactive-Loaded Hydrogels for Wound Care: From Formulation to Clinical Translation - A Review

Abstract

Chronic wounds continue to pose a major challenge to global healthcare systems due to their prolonged healing time and complex pathology. While developed nations face substantial economic burdens from wound management, developing countries encounter additional difficulties related to higher prevalence and limited access to advanced treatments. In this context, the incorporation of plant-derived bioactive compounds into three-dimensional hydrogel systems has emerged as a promising strategy for effective wound care. These bioengineered hydrogels offer multifunctional benefits by simultaneously targeting microbial infections, controlling inflammation, and enhancing tissue regeneration in both acute and chronic wounds. This review focuses on recent advancements in natural bioactive-based hydrogel wound dressings, highlighting plant-derived compounds such as curcumin, Aloe vera, Centella asiatica, quercetin, calendula, and berberine. These compounds are incorporated into polymeric matrices composed of materials like chitosan, alginate, gelatin, polyvinyl alcohol, and hyaluronic acid. Such systems can respond to environmental stimuli, including pH variations, temperature changes, and reactive oxygen species, enabling controlled and sustained release of therapeutic agents. Their synergistic interactions enhance antimicrobial efficacy while also supporting angiogenesis and collagen synthesis, thereby improving healing outcomes and reducing dependence on costly synthetic drugs. Emerging technologies such as self-assembling peptide hydrogels, targeted drug delivery systems, and nanoparticle-assisted biofilm disruption are expanding the scope of personalised wound care solutions. A rigorous evaluation through standardised testing protocols and clinical studies is essential to assess parameters such as stability, mechanical strength, biocompatibility, and therapeutic efficacy. These efforts facilitate regulatory approval and the translation of laboratory research into clinical application. This review consolidates current knowledge and provides practical guidelines for the development and characterisation of natural bioactive-loaded hydrogels. It also outlines future research directions for designing cost-effective, efficient, and widely accessible wound-healing systems.

Introduction

The text explains the complex biological process of wound healing and how bioactive-loaded hydrogel dressings can improve treatment, especially for chronic and non-healing wounds.

Wound healing occurs in four overlapping phases: hemostasis, inflammation, proliferation, and remodeling. It begins with blood clot formation and immune response, followed by tissue regeneration involving fibroblasts, collagen production, angiogenesis, and skin cell repair. The final remodeling phase strengthens the tissue, but healed skin still remains weaker than normal skin. When this process fails, it leads to chronic wounds, which are a major medical and economic burden worldwide.

To improve healing, the text highlights the use of hydrogels, which are water-rich, 3D polymer networks that mimic natural tissue and maintain a moist environment that supports cell growth and prevents infection. Their properties—such as moisture control, biocompatibility, and controlled degradation—make them ideal for wound care. Research shows that hydrogel degradation can even enhance the release of healing factors like VEGF, improving blood vessel formation and tissue regeneration.

The review also emphasizes the role of natural plant-based bioactive compounds such as Aloe vera and Centella asiatica, which have strong wound-healing, anti-inflammatory, and collagen-boosting properties. Clinical studies show they can speed up healing, reduce pain, and improve recovery without significant side effects.

Different hydrogel polymers like alginate, gelatin, carboxymethyl cellulose (CMC), and polyvinyl alcohol (PVA) are discussed for their specific benefits, including antibacterial action, moisture retention, biocompatibility, and mechanical strength. Advanced multi-network hydrogels further enhance performance for complex wound environments.

References

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Copyright © 2026 Kiruthika A. R., Jancy Mary E.. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.