PRP Scaffolds in Chronic Wound Care: A Move Toward Regenerative Solutions

Diabetic foot ulcers, venous leg ulcers, and pressure ulcers continue to pose significant clinical challenges. These wounds often stall in the inflammatory phase, driven by oxidative stress, protease overactivity, and senescent or dysfunctional cells. In the context of diabetes, impaired stem cell function and poor vascularization further delay healing. Conventional measures such as debridement, compression, and negative pressure therapy can help, but rarely achieve consistent closure.

This gap has fueled interest in regenerative medicine. A review published in Regenerative Therapy in June 2025 highlights platelet-rich plasma (PRP) as a particularly promising strategy. PRP, an autologous concentrate of platelets and growth factors, can stimulate angiogenesis, collagen deposition, and re-epithelialization. However, direct injection is hampered by short bioavailability and inconsistent release, so embedding PRP within scaffold systems has emerged as a way to sustain its activity and amplify its impact.

Here's a quick look at how these scaffolds work and their potential clinical significance.

The Function of PRP Scaffolds

Scaffolds made from natural, synthetic, or composite biomaterials provide structural stability, biocompatibility, and controlled release of growth factors. Gel formation with thrombin or calcium chloride creates fibrin networks while activating platelets, lyophilization extends shelf life while retaining bioactivity, and chemical cross-linking produces hydrogels with tunable strength and release profiles. Integration with stem cells or exosomes further enhances regenerative capacity.

The effects of PRP scaffolds are broad. They can upregulate cyclins and anti-apoptotic proteins, promoting fibroblast and endothelial proliferation while accelerating keratinocyte migration. Some studies have reported that sustained VEGF and TGF-β1 release supports angiogenesis, confirmed by CD31 staining of new vessels. PRP-scaffolds have also been associated with immunomodulatory activity, including promotion of M2 macrophage polarization, reduced IL-6 and TNF-α, and increases in IL-10 and IL-1ra. In other investigations, scaffolds incorporating PRP enhanced collagen organization, while combinations with chitosan or ε-poly-L-lysine provided antibacterial protection against common wound pathogens. Several designs have further demonstrated mechanical resilience, retaining tensile strength and elasticity while supporting prolonged release of bioactive factors.

Emerging Designs

Hybrid systems are also helping to push the field forward. Methacrylate gelatin and methacrylated silk fibroin (GelMA/SFMA) hydrogels, created by photo-crosslinking, boost adipose-derived stem cell proliferation and accelerate wound closure in murine pressure ulcer models. Collagen-PRP scaffolds enriched with adipose-derived stem cell exosomes mimic the extracellular matrix, improve re-epithelialization, and dampen inflammation. These designs exemplify how biologics and biomaterials can be combined to recreate the conditions for healing.

Clinical Impact

PRP scaffolds are biocompatible, versatile, and have shown encouraging results in preclinical studies, with benefits ranging from controlled release of growth factors to antimicrobial protection. However, important limitations remain, including variability in PRP preparation methods, uncontrolled early release of growth factors, and mechanical weaknesses in load-bearing applications. Additionally, evidence from long-term clinical trials is still limited.

For translation into real-world therapies, progress may depend on standardized PRP preparation protocols, the use of advanced fabrication techniques such as 3D printing and electrospinning, and integration of nanotechnology for more precise and responsive delivery. Equally important will be large, well-powered clinical trials to establish safety and efficacy, alongside cost-effectiveness analyses to support broader accessibility.

Reference:

Altalbawy FMA, Mukhlif BAM, Hussen A, et al. Regenerative potential of PRP-based scaffolds in chronic wound healing: Mechanisms, advances, and therapeutic insights. Regen Ther. 2025;30:278-298. Published 2025 Jun 26.