Polymeric Composite Dressings Containing Calcium-Releasing Nanoparticles Accelerate Wound Healing in Diabetic Mice

Abstract

Objective: Wound healing is a complex process that involves the interaction between different cell types and bioactive factors. Impaired wound healing is characterized by a loss in synchronization of these interactions, resulting in nonhealing chronic wounds. Chronic wounds are a socioeconomic burden, one of the most prominent clinical manifestations of diabetes, however, they lack satisfactory treatment options. The objective of this study was to develop polymeric composites that deliver ions having wound healing properties and evaluate its performance using a pressure ulcer model in diabetic mice. Approach: To develop a polymeric composite wound dressing containing ionreleasing nanoparticles for chronic wound healing. This composite was chemically and physically characterized and evaluated using a pressure ulcer wound model in diabetic (db/db) mice to explore their potential as novel wound dressing. Results: This dressing exhibits a controlled ion release and a good in vitro bioactivity. The polymeric composite dressing treatment stimulates angiogenesis, collagen synthesis, granulation tissue formation, and accelerates wound closure of ischemic wounds created in diabetic mice. In addition, the performance of the newly designed composite is remarkably better than a commercially available dressing frequently used for the treatment of lowexuding chronic wounds. Innovation: The developed nanoplatforms are cell-and growth factor free and control the host microenvironment resulting in enhanced wound healing. These nanoplatforms are available by cost-effective synthesis with a defined composition, offering an additional advantage in potential clinical application. Conclusion:Based on the obtained results, these polymeric composites offer an optimum approach for chronic wound healing without adding cells or external biological factors.

Acceleration of Wound Healing through Amorphous Calcium Carbonate, Stabilized with High-Energy Polyphosphate

“…A similar strategy in wound treatment has not been addressed before (for a review of current materials, see [ 4 ]). Other strategies, e.g., based on the use calcium-releasing nanoparticles such as CaP ormoglass (organic modified calcium phosphate glass; [ 37 ]) also showed an accelerating effect on chronic wound healing [ 40 ], but these strategies lack the energy-providing effect of polyP. In principle, polyP alone in the form of Ca-polyP nanoparticles has also a stimulatory effect on wound healing, as shown previously [ 22 ]; however, in this case, after the ALP-mediated degradation of this molecule, no calcium-releasing store remains that can maintain the wound-healing effect of calcium ions.…”

“…In addition, calcium is a stimulator of angiogenesis both in vitro and in vivo [ 35 , 36 , 37 ]. The acceleration of wound healing, especially in chronic wounds, has been demonstrated by the use of calcium alginate dressings [ 38 , 39 ] or dressings containing calcium-releasing nanoparticles [ 40 ].…”

Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications

“…Moreover, DFO and copper synergistically upregulated the expression of HIF-1α and VEGF, thereby regulating angiogenesis [ 167 ]. Soledad Perez-Amodio et al prepared poly(lactic acid) (PLA) fiber matrices loaded with calcium-releasing nanoparticles (SG5) (PLA-SG5) and experimentally demonstrated that this compound material stimulates angiogenesis, collagen synthesis, and granulation tissue formation and accelerates wound closure in the ischemic wounds of diabetic mice [ 264 ]. Of note, the metals mentioned above can avoid drug resistance and promote wound healing through different mechanisms.…”

Quantification of extracellular matrix components in immunolabeled tissue samples

“…• Timing 26 hours, 1.5-hours hands-on time 24. Collect mice wound healing assay tissue samples by tissue excision 14 days after generation of pressure ulcers (6 days) and wound treatment (8 days) with poly-lactic acid (PLA) or Mepilex® (Control) wound dressings, following the protocol described by Pérez-Amodio et al 46 . 25.…”