Preparation and Assessment of Novel Chitosan/Bioactive Glass Composite Foams for Exudate Management in Wound Dressing Applications

Abstract

Although biocomposite foams have been used as wound dressings, achieving accelerated healing with reduced complications requires precise control of exudate absorption and evaporation. This study evaluated the fluid handling capacity, water vapor transmission, and cytotoxicity of novel chitosan/bioactive glass composite foams. Prepared following a simple process, these foams have up to 60% porosity and interconnected pore networks. Cytotoxicity assays confirmed their non-toxicity to L-929 fibroblast cells. The foams demonstrated a liquid absorption capacity of up to 160%, with improved performance at higher levels of bioactive glass. Fluid handling tests showed effective moisture absorption and transfer, making these dressings suitable for the treatment of wounds such as burns and pressure ulcers. The water vapor transmission test confirmed the ability of the foams to promote high exudate removal rates, suggesting that chitosan/bioactive glass composites are promising for wound dressing applications.

Keywords:
Chitosan; Bioactive glass; Foams; Wound dressing; Fluid handling; Cytotoxicity

1. Introduction

Skin wounds are tissue abnormalities caused by disease or injury, resulting in loss of tissue integrity and/or functionality¹. Under normal conditions, the healing process proceeds in an orderly fashion through the stages of hemostasis, inflammation, proliferation, and maturation (or remodeling)²-⁴. However, dermatologic disorders often manifest as partial- or full-thickness injuries, including burns or chronic wounds, which can result in hypertrophic scars and keloids³,⁵. In addition, deregulated immune function due to factors such as excessive moisture, a warm wound bed, and inadequate wound perfusion can promote the accumulation of devitalized, ischemic, hypoxic, or necrotic tissue, creating an optimal environment for secondary infection⁶,⁷. As a result, the development of effective wound dressings is essential to improve the healing of chronic wounds and reduce the burden of this public health problem.

Controlling the adsorption of wound exudate and facilitating blood clotting are critical to achieving rapid and complete wound healing⁷,⁸. As a result, wound dressings must meet a delicate balance between preventing excessive exudate, which can cause infection or maceration, and maintaining optimal moisture to promote healing and minimize scarring⁹,¹⁰. Therefore, it is critical to develop dressings that can partially absorb wound exudate and promote subsequent fluid evaporation¹¹,¹². This property is particularly important for surgical dressings, as it reduces the need for frequent dressing changes during surgery, and also for wounds with high levels of exudate¹³. Traditional wound dressings are available as semipermeable films, foams, hydrogels, and hydrocolloids¹⁴-¹⁶. Nonetheless, recent advances in tissue engineering offer an alternative to traditional wound dressing materials, worth highlighting the development of bioactive wounds. The porous nature of these materials allows for effective fluid handling, while their bioactive properties can enhance biological fixation and promote cell growth.

Polymers, which often offer excellent processability and customizable mechanical properties, have been widely used in the preparation of bioactive wounds¹⁷-²⁰. Various synthetic polymers have been used for this purpose, including polylactic acid, polyglycolic acid, polyanhydrides, poly(ortho esters), polycaprolactone, polycarbonates, and polyfumarates. However, the properties required for use in wound dressing systems, particularly biocompatibility, may not be fully met by these polymers. Addressing these challenges requires further research and technological advances²¹-²⁴. Wound dressings based on natural polymers such as alginate, collagen, and chitosan (CH)⁸,¹⁵,²⁵,²⁶ have been investigated in recent years and have shown improved properties compared to synthetic polymers, mainly due to their similarity to biological macromolecules. When used as a wound dressing, these materials have been shown to have the ability to accelerate the formation of granulation tissue and epithelialization, thereby facilitating a more efficient tissue repair²⁷-²⁹. In particular, CH foams have demonstrated significant potential as wound dressings due to their unique combination of properties, including biocompatibility, biodegradability, high water absorption, antimicrobial activity, and strong adhesion³⁰-³⁹. However, under physiological conditions, CH foams typically exhibit limited mechanical strength and rapid degradation rate⁴⁰-⁴³. As a consequence, the incorporation of bioceramics into CH to obtain composite foams has been explored to improve their mechanical behavior and bioactivity⁴⁴,⁴⁵.

Bioactive glasses (BGs) are a promising class of inorganic materials that can actively interact with physiological fluids. In particular, BGs exhibit antimicrobial properties that can improve the efficacy of materials used to treat skin wounds by promoting local angiogenesis and stimulating healing processes⁴⁶-⁴⁸. Initially developed by Hench et al.⁴⁹ in the early 1970s, BGs have since evolved through variations in synthesis methods, resulting in a range of biomaterials with tailored properties. The glass originally prepared by Hench's team belongs to the SiO₂-CaO-P₂O₅-Na₂O system and has the following composition (wt%): 45% SiO₂, 24.5% CaO, 24.5% Na₂O, and 6% P₂O₅. This glass has traditionally been synthesized by the melt-quenching method, in which a powder mixture is melted at high temperatures, held for up to 24 h, and then rapidly cooled to room temperature to prevent crystallization. Alternatively, the sol-gel process has emerged as a popular synthesis route for BGs, allowing control over chemical composition, homogeneity, particle size, and pore structure⁵⁰-⁵³. Sol-gel-derived materials are inherently porous and have a larger specific surface area than melt-quenched glasses. In this study, we used 58S bioactive glass with a composition of 58 wt% SiO₂, 33 wt% CaO, and 9 wt% P₂O₅, which was synthesized by the sol-gel method. This composition is particularly reactive in aqueous environments due to its higher CaO content and CaO/P₂O₅ ratio. The degradation products of 58S BG are reported to increase intracellular alkaline phosphatase activity⁵⁴, a marker associated with collagen fiber regeneration in fibroblasts. In skin injury, increased phosphatase activity in fibroblasts is associated with the formation of regenerative collagen fibers⁵⁵,⁵⁶. These properties make sol-gel-derived 58S BG an excellent choice for our research.

In previous studies, we described the mechanical behavior of CH/BG composite foams. We found that CH foams with up to 50 wt% BG exhibited a significant increase in Young's modulus and mechanical strength, as well as enhanced shape recovery capacity. In addition, the degradation rate decreased after the incorporation of BG into the foams compared to pure CH⁴⁸,⁵⁷. However, more research is needed on the properties of composites for wound dressing applications. In this study, we prepared CH/BG composite foams using a simple and rapid method. We evaluated the effect of incorporating BG into CH foams on their pore structure, fluid handling capacity, and cytotoxicity. Our findings contribute to the development of dressings with enhanced exudate exchange for the treatment of chronic wounds.

2. Experimental

2.1. Syntheses

2.1.1. Starting materials

All reagents used were analytical grade, and Milli-Q water (18.2 MΩ.cm at 25°C) was used in all solutions. CH powder (M_W = 320,000 g/mol, degree of deacetylation > 75%, Sigma-Aldrich) was used without further purification. Adipic acid (C₆H₁₀O₄, 99.8%) was obtained from Vetec Química. BG was synthesized using tetraethyl orthosilicate (TEOS, C₈H₂₀O₄Si, Aldrich), nitric acid (HNO₃, Merck), triethyl phosphate (TEP, C₆H₁₅O₄P, Merck), and calcium nitrate tetrahydrate (Ca(NO₃)₂·4H₂O, Synth). Glycerol (GLY, ≥ 99.5%, Aldrich) and sodium lauryl ether sulfate (SLES, ≥ 99%, Aldrich) were used to prepare the foams.

2.1.2. Preparation of BG particles and CH/BG foams

BG 58 S powder with a nominal composition of 60 mol% SiO₂, 36 mol% CaO, and 4 mol% P₂O₅ was prepared via a sol-gel alkoxide route⁵⁸. Briefly, a mixture of H₂O (132.2 mL), HNO₃ (2 M, 22.4 mL), TEP (13.75 mL), and TEOS (137.1 mL) was initially prepared under stirring at room temperature for 60 min. Ca(NO₃)₂.4H₂O was then added dropwise and the resulting solution was stirred for another 30 min. It was then poured into sealed Teflon flasks and aged at 60 °C for 72 h. The flasks were opened and the gel was dried, starting at 60 °C and increasing by 10 °C every 24 h until 120 °C was reached. This step was followed by a heat treatment in air at 700 °C for 3 h at a heating rate of 2 °C/min. The resulting solid was then ground and sieved to obtain particles in the size range of 38-150 μm.

The preparation of the CH/BG composite foams began with the preparation of a 3% (wt/vol) solution of CH in H₂O containing 1% C₆H₁₀O₄, which was stirred at room temperature for 24 h. The pH of the solution was adjusted to 5.5 ± 0.1 using 1.0 M NaOH while stirring at 40 °C for 1 h. This step ensured the complete dissolution of the components and yielded a clear solution. Flexible 3D composite foams were then obtained by a combination of the CH aqueous solution with BG microparticles as described in Table 1. The equivalent of 10 wt% GLY was added to all foams. For pure CH foam, GLY was incorporated directly into the CH solution. For the composite foams, GLY served as a dispersant for the BG particles and was mixed with these particles before incorporation into the CH solution. In addition, SLES was added to all compositions. The mixture was stirred vigorously until a stable foam was obtained. This foam was then poured into silicone containers and frozen at -20 °C for 48 h. It was then air-dried at 55 °C for 24 h.

Table 1
Composition of composite foams prepared in this work.

Sample	Composition (wt%)
	CH	BG
CHF	100	0
CH25BGF	75	25
CH50BGF	50	50

2.2. Evaluations

2.2.1. Structural characterization

Fourier transform infrared (FTIR) spectroscopy was performed using a Thermo Scientific Nicolet 6700 spectrometer in the attenuated total reflectance (ATR) mode. The spectral range was 4000-650 cm^-1 with a resolution of 4 cm^-1 and 64 scans. X-ray diffraction (XRD) was performed using a Shimadzu 7000 powder X-ray diffractometer with CuKα radiation (λ = 1.54 Å), operating at 40 kV and 30 mA. The XRD patterns were collected in a 2θ range of 5-90°. Morphological analyses were performed by scanning electron microscopy (SEM) on a Shimadzu SSX-550 microscope at an accelerating voltage of 15 kV. The samples were previously deposited on double-sided carbon tapes and sputter-coated with carbon. X-ray microtomography (micro-CT) was performed using a Bruker SkyScan 1174 system with a source voltage of 40 kV and a source current of 800 µA. Imaging was performed with a pixel size of 17 µm and no filters were used. The resulting shadow projections (in 16-bit TIFF format) were reconstructed into 2D slices using the NRecon software interface. CTAnalyser software was used for 3D analysis and surface rendering, while CTvol software was used for 3D volumetric visualization. All software was provided by the micro-CT supplier.

2.2.2. Fluid transport properties

To determine Fluid Absorption Capacity (FAC – %), samples were first weighed and then soaked in a 20 mL buffer solution at 37 °C and pH 7.4 for up to 24 h. After soaking, the samples were removed from the solution and excess water was removed using a wet filter paper. The samples were then reweighed to determine the wet weight. FAC was calculated using Equation 1, where M_i is the initial/dry mass (g) and M_f is the final/wet mass (g). Tests were performed in triplicate.

$\text{FAC =}\frac{{\text{M}}_{\text{f}}-{\text{M}}_{\text{i}}}{{\text{M}}_{\text{i}}}\text{×100}$ (1)

Water Vapor Transmission (WVT – g/h.cm²) was determined according to ASTM E96/E96M-10 (Standard Test Methods for Water Vapor Transmission of Materials). Samples with an area of 4.9 cm² and a thickness of 0.6 mm (both dry and wet) were fixed in Paddington cups containing 10 mL of simulated wound exudate (SWE) consisting of 142 mM NaCl and 2.5 mM CaCl₂. The opening in the Paddington Cups, through which the samples were attached, allowed vapor permeation through the material. The Paddington cups were then weighed and stored in glass desiccators containing silica gel particles at room temperature. After a period ranging from 24 h to 120 h, the samples were reweighed, and WVT was determined using Equation 2). This equation normalizes WVT to a 24-h period, where "g" is the mass of water permeated through the sample, "t" is the time (h), and "a" is the permeation area (cm²). Experiments were performed in triplicate to ensure accuracy and consistency.

$\text{WVT =}\frac{\text{g × 24}}{\text{t × a}}$ (2)

Fluid Handling Capacity (FHC – g/h.cm²) was evaluated using an SWE following the protocol outlined in the British Standard BS EN 13726-1:2002 (Test methods for primary wound dressings - Aspects of absorbency). Dry samples were attached to custom permeability cups. These cups were divided into two sections: one for water deposition and the other with an opening to allow fluid permeation through the sample. Each cup was filled with 20 mL of SWE, and the hydrogels were securely attached. A piece of nylon mesh with the same diameter as the sample was added to each hydrogel for additional mechanical support. The assembled setups were then weighed and inverted in a desiccator containing dehydrated silica gel, maintained at 37 °C. Samples were reweighed after 24 h. These values were used to calculate the Water Vapor Transmission Rate (WVTR – g/h.cm²) and Absorption Capacity (ABS – g/h.cm²) using Equations 3 and 4, respectively. In these equations, "x" represents the initial system mass, "y" represents the system mass after 24 h, "b" represents the initial foam mass, and "a" represents the foam mass after 24 h. As shown in Equation 5, FHC is the sum of WVTR and ABS.

$\text{WVTR =}\frac{\text{x}-\text{y}}{\text{Storage time × area}}$ (3)

$\text{ABS =}\frac{\text{b}-\text{a}}{\text{Storage time × area}}$ (4)

$\text{FHC = WVTR + ABS}$ (5)

2.2.3. In vitro assays

The MEM-elution assay was performed according to the guidelines of ISO 10993-5 (Biological Evaluation of Medical Devices; Part 5: Tests for Cytotoxicity: In Vitro Methods). For all assays, L-929 mammalian fibroblast cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with fetal bovine serum (FBS) at a concentration of 10 vol%, streptomycin sulfate (10 mg/mL), penicillin G sodium (10 units/mL), and amphotericin-B (0.025 mg/mL), all from Gibco BRL (NY, USA). Cell cultures were maintained in a 5% CO₂ humidified atmosphere at 37 °C. L929 cells (suspended at 10⁵ cells/1.5 mL) were seeded on 35‑mm dishes and incubated for 72 h. Triplicate extracts of ethylene oxide-sterilized samples (CHF, CH25BGF, or CH50BGF), along with negative controls (high-density polyethylene - HDPE) and positive controls (latex), were prepared by exposure to DMEM-10 vol% FBS solution for 72 h. The culture media of confluent L-929 monolayers were then replaced with the different eluates and the cultures were incubated for another 48 h. The eluates were then removed and the cultures were examined microscopically after staining with crystal violet (2% in 20% ethanol) to detect morphological changes, density changes, and cell lysis induced by the tested materials. The cytotoxicity score was assigned according to ISO 10993-5 guidelines, ranging from 0 (without toxicity) to 4 (maximal damage to the cell monolayer). Prism software (GraphPad Software, San Diego, USA) was used for one-way analysis of variance (ANOVA) followed by the Bonferroni test for multiple comparisons. A p-value less than 0.05 was considered statistically significant. All analyses were performed in triplicate to ensure robustness and reliability.

3. Results and Discussion

Figure 1a shows the FTIR spectra of CH, BG, and CH-BG composite foams prepared in this study. For CH (Figure 1a-A), the amide I absorption band, primarily associated with C=O stretching, is observed at about 1650 cm-1 ⁵⁹,⁶⁰. The amide II band, attributed to N-H and C-N bending, is detected around 1550 cm-1 ⁶¹. The C-O-C stretching, which is related to the saccharide structure, is found at 1150 cm^-1 and 895 cm-1 ⁶²,⁶³. The absorption band at 1040 cm^‑1 corresponds to the C-O stretching⁶⁴. In the BG spectrum, the band centered at about 1080 cm^‑1 is associated with the stretching vibration of phosphate groups (PO₄^3-)⁶⁵. An absorption band related to Si-O stretching is detected at 995 cm^-1, and a band due to Si-O-Si stretching is observed at 756 cm-1 ⁶⁵-⁶⁷. The CH/BG composite foams (Figure 1C) show bands at about 1150 cm^-1 and 1040 cm^-1, corresponding to C-O-C of the saccharide structure and cyclic C-O, respectively⁶⁸. In addition, they exhibit bands at 1315 cm^-1 and 1270-1210 cm^-1, corresponding to N-H (I) and N-H (II) deformation, respectively⁴¹,⁶⁸. All composite foams show bands related to amide II, indicating the presence of chitosan. However, this band was shifted from about 1550 cm^-1 to 1540 cm^‑1 in CH50BGF (Figure 1a-E). Hydrogen bonding between N-H(II) groups of CH and surface Si-OH groups of BG may be responsible for this band shift. Additional shifts occur in the vibration associated with the stretching of the carbonyl (C=O) of amide I with the carboxylate group of adipic acid, causing the bands to overlap. The carbonyl band located at 1638 cm^-1 in CHF is also shifted in the composite foams to 1577 cm^-1, probably due to hydrogen bonding between the silanol and C=O groups of CH. As a result, the stretching constant decreases, resulting in a lower stretching wavenumber⁶⁹.

Figure 1
(a) FTIR spectra, (b) XRD patterns, and (c) SEM micrographs of (A) CH, (B) BG, (C) CHF, (D) CH25BGF, and (E) CH50BGF. The scale bars shown in the SEM images correspond to 100 μm.

Figure1b shows the XRD patterns obtained in this study. The XRD pattern of pure CH (Figure 1b-A) shows two prominent diffraction peaks at about 2θ = 10° and 20°, which are indicative of semicrystalline CH⁷⁰,⁷¹. The prominent peak at 20° has been attributed to the (001) and (100) crystal planes of the monoclinic system⁷². In contrast, the XRD pattern of BG (Figure 1b-A) is characterized by a broad halo centered around 28°, indicating it is predominantly amorphous. The amorphous structure of BG plays a crucial role in improving its biological properties, in particular by increasing its dissolution rate and biocompatibility. With no evidence of a crystalline phase, the composite foams exhibit XRD patterns that reflect contributions from both CH and BG. Figure1c displays SEM micrographs of the composite foams, which reveal a network of interconnected pores. CHF exhibited a broad pore size distribution ranging from 115 µm to 450 µm. On the other hand, CH25BGF and CH50BGF exhibited narrower pore size distributions, ranging from 115 µm to 270 µm for the former and from 160 µm to 260 µm for the latter. Electrostatic interactions between CH and BG are probably responsible for the observed structural difference. These interactions can inhibit the growth and release of air bubbles formed during the mixing of CH and BG, thereby reducing the pore size in BG-containing samples⁴⁸. Ensuring that the pore size and interconnectivity are suitable for cell adhesion, cell migration, and fluid management is critical when evaluating materials for use in tissue engineering and wound healing applications⁷³. The homogeneous macroporous network observed in this study is well suited for exudate management, allowing cells and water molecules to migrate through the dressing, thereby maintaining the optimal moisture levels required for effective wound healing.

Figure 2 shows representative 3D models obtained by micro-CT. CHF showed a total porosity of 45 ± 3% and an average pore size of 249 ± 8 µm. In contrast, CH25BGF displayed a total porosity of 60 ± 6% with an average pore size of 269 ± 8 µm, while CH50BGF exhibited a total porosity of 52 ± 1% and an average pore size of 150 ± 2 µm. Also consistent with the SEM results (Figure 1), all samples exhibited a highly interconnected pore network with more than 98% open pores. The high porosity and interconnected pore structure of the dressing are critical for tissue regeneration and vascularization. These properties also improve wound exudate flow, which is critical to the effectiveness of wound dressings. Non-occlusive or semi-occlusive dressings with high porosity facilitate fluid exchange during wound healing and reduce the need for frequent dressing changes. This feature is particularly valuable for full-thickness wounds because it minimizes patient discomfort associated with dressing changes²,⁶,⁷⁴.

Figure 2
3D models obtained by micro-CT for (A) CHF, (B) CH25BGF, and (C) CH50BGF. The scale bars shown in these images correspond to 200 μm.

Figure 3 shows the fluid absorption behavior evaluated for CHF, CH25BGF, and CH50BGF. All samples exhibited initial rapid uptake within the first hour, followed by stabilization. Notably, CH50BGF exhibited higher fluid absorption, reaching about 160% after 24 h. The significant absorption capacity observed in all samples is due to their high porosity and interconnected pore network, as demonstrated by SEM and micro-CT (Figures 1 and 2). In comparison, previous studies have reported that non-porous hydrogel films composed of low-methoxyl pectin, gelatin, and carboxymethylcellulose have fluid uptake capabilities of up to 90%⁷⁵. However, the FAC values observed in our work, facilitated by the porous structure of the foam, exceed these values. In addition, the inherent ability of CH to interact with H₂O due to its amino groups contributes to its high water absorption and swelling capacity. It is also evident that FAC increases with BG content, an indication of the influence of glass loading on the water absorption capacity of the foam. This can be attributed to the high concentration of surface silanol groups (Si-OH) on BG⁷⁶, which are hydrophilic and enhance the interaction of the dressing with water.

Figure 3
Fluid absorption capacity evaluated for CHF, CH25BGF, and CH50BGF foams in pH 7.4 buffered solution for up to 24 h.

The substantial FAC of the composites prepared in this study validates their potential application in the treatment of highly exuding wounds. The process of fluid absorption involves three primary steps; 1) diffusion of solvent molecules within the polymer network; 2) relaxation and increased spacing between polymer chains caused by hydration; and 3) expansion of the 3D matrix network⁷⁵,⁷⁷. This process is closely related to the cross-linking density and mechanical strength of the polymer⁷⁸. In 3D porous scaffolds, a portion of the fluid is also used to fill the pores, which is influenced by the porosity of the material. Therefore, fluid absorption assays play a critical role in assessing the ability of the scaffold to absorb exudate and determining the time at which this absorption reaches maximum saturation. These properties are of paramount importance when considering biomaterials for applications in skin wounds. In particular, Figure 3 shows that CH50BGF reached a FAC of 160% after 24 h, a result that exceeds those reported in the existing literature and therefore deserves attention.

Measuring WVT is a critical feature for wound dressings. Increased water permeability not only favors the establishment of optimal moisture levels in the wound area, but also promotes cell migration⁷⁹. It also assists in categorizing 3D matrices as occlusive or vapor permeable. Thus, the study of WVT proves to be a valuable tool in determining the ideal wound type for the developed device, given the variability in exudate release rates between different wounds. Figure4 shows the WVT variance over time. This test was initially performed using the standard method on dried samples. These initial test results showed high WVT values, especially for CH25BGF and CH50BGF. However, a significant variance in WVT over time was observed as shown in Figure 4a. The first 24 h represented the period of highest WVT, followed by a gradual decrease over the next few days. This high value is due to greater water vapor absorption by the dry porous materials, resulting in foam saturation within the first 24 h, followed by stabilization. The 3D models obtained by micro-CT showed that the composite foams had similar porosity. This structural similarity likely contributed to the similarity in WVT values observed for CH25BGF and CH50BGF after the first 24 h as the dried samples reached equilibrium. The indistinguishable WVT values between these composites, even within standard deviations, underscore the strong influence of total porosity on moisture transfer properties. These results suggest that since higher or more uniform porosity can facilitate uniform vapor diffusion throughout the material, the porosity distribution is a key factor in determining the moisture management capacity of foams. The samples developed in this study are designed to treat skin wounds, which typically require a moist environment for healing. Consequently, the primary objective of these foams, when used as dressing devices, is to partially absorb wound exudate. Examining materials under conditions that simulate direct application in exudate has been reported to be important⁸⁰. For this reason, WVT tests have been carried out on wet foams to replicate real application scenarios and the results are shown in Figure 4b. Compared to dry samples, moistened specimens showed reduced WVT values. Additionally, the results showed improved consistency of release values, characterized by a reduced standard deviation, close to values reported in previous studies⁸¹. These results are consistent with those reported by Thomas and Young⁸⁰, who studied epithelial water loss by evaporation under severe injuries. The differences observed between the results for samples with and without BG can be attributed to two factors: the higher porosity of the composite foams and consequently higher permeability compared to the pure CH foam, and the high concentration of Si-OH groups on BG. These chemical groups, together with the amino groups from CH, increase the degree of interaction of the composite sample with water. These results confirm those observed in the fluid absorption tests (Figure 3). Dressings with low WVT values can lead to three clinically undesirable conditions¹: occlusion and resistance to water vapor escape, increasing pressure at the injury site²; fluid leakage through the edges of the dressing, which can cause maceration of the injured tissue and delay in scar formation, resulting in pain and discomfort for the patient³; elevation of the edges of the dressing, exposing the wound and increasing the risk of microbial entry and secondary infection⁸⁰,⁸²-⁸⁴. Based on the results of this study, the scaffolds produced here are well suited for use in wounds characterized by high levels of exudate, such as third-degree burns and granulation tissue in chronic pressure ulcers. These scaffolds effectively maintain the optimal local moisture required for an efficient healing process.

Figure 4
Water vapor transmission as a function of time for (a) dried and (b) moistened samples of CHF, CH25BGF, and CH50BGF.

The absorption of exudate and its subsequent evaporation from the wound bed into the surrounding environment are critical parameters to consider when developing new systems to cover and facilitate the regeneration of skin wounds⁸⁵. The FHC assay allows the evaluation of topical coverage under continuous fluid contact, more closely simulating the application of a dressing to a skin injury. This is especially important in severe cases where exudate production can be up to 1 g per cm² per day⁸⁰. In this study, the FHC test was performed to evaluate the absorbency and permeability of the matrices when in contact with a SWE solution. FHC can be calculated as the sum of ABS and WVTR⁸⁶. The results obtained are given in Table 2. The WVTR values obtained ranged from 1.9 ± 0.1 to 3.2 ± 0.7 g/10 cm²/24 h, which is in line with previously reported values for CH-based dressings⁸⁶,⁸⁷. Notably, CH50BGF had a higher absorbency, similar to commercial dressings such as Allevyn Adhesive^®, which had an absorbency of 4.32 g/10 cm²/24 h⁸⁰. FHC values ranged from 4.3 ± 0.6 g/10 cm²/24 h for CHF to 7.2 ± 0.7 g/10 cm²/24 h for CH50BGF. These values are consistent with those observed in full-thickness burns and pressure ulcers, where exudate production typically ranges from 3 to 5 g/10 cm²/24 h¹¹,⁸⁰,⁸¹. The results obtained from the FHC and WVT assays corroborate each other, with higher values observed for samples containing BG. This behavior may be due to the presence of hydrophilic Si-OH groups from BG and the higher porosity of CH25BGF and CH50BGF in comparison to CHF. These factors increase the interaction of these samples with the simulated wound exudate, allowing for greater absorption and permeability. Overall, the results confirm that the foams produced are effective in absorbing and transferring moisture from wounds. As a result, they appear to be promising materials for the treatment of full-thickness burns and pressure ulcers, promoting an optimal moisture environment in the wound bed and aiding the healing process.

Table 2
Means and standard deviations of moisture vapor transmission rate (MVTR*), absorption capacity (AC*), and fluid handling capacity (FHC*) for the prepared foams.

Sample	MVTR*	AC*	FHC*
CHF	1.9 ± 0.1	2.3 ± 0.7	4.3 ± 0.6
CH25BGF	2.5 ± 0.3	2.4 ± 0.5	4.9 ± 0.4
CH50BGF	3.2 ± 0.7	4.0 ± 0.7	7.2 ± 0.7

• ^*
  g/10cm²/24hours

Table 3 shows the cytotoxicity levels determined by the MEM elution assay, while Figure 5 shows histological staining under an inverted light microscope after 72 h of incubation, with viable cells indicated by purple staining. Reduced cell viability is observed for CHF (reactivity level = 1) compared to BG-containing samples, although all samples are non-toxic to L-929 mammalian fibroblast cells. It is important to note that BGs have been reported to affect both cell adhesion and proliferation⁸⁸, as noted in previous studies. It has been reported these materials can accelerate skin regeneration by enhancing angiogenesis and collagen deposition in the proliferation phase, as well as having positive effects on all other important phases of wound healing⁸⁹. These effects could potentially affect cell viability, as evidenced in this study. Further studies are needed to evaluate their efficacy in the clinical setting and to optimize their performance for specific wound types.

Table 3
Cytotoxicity levels determined by in vitro elution assays after 72 h of cell incubation.

Material	Reactive degree
None material	0
HD Polyethylene	0
Latex	4
CHF	1
CH25BGF	0
CH50BGF	0

Figure 5
Histological staining of L-929 mammalian fibroblast cells after 72 hours of cell incubation in contact with samples (a) cells only; (b) HDPE - negative control; (c) latex - positive control; (d) CHF; (e) CH25BGF; and (f) CH50BGF. The scale bars shown correspond to 100 μm.

4. Conclusions

In this work, highly porous CH and BG composite foams were successfully obtained. SEM analysis revealed that the foams exhibited interconnected pore networks, with CHF having a broader pore size distribution compared to CH25BGF and CH50BGF. This difference is attributed to electrostatic interactions between CH and BG that influence pore size and distribution. Micro-CT imaging confirmed the highly porous nature of the dressings, with all samples exhibiting interconnected pore networks that promote tissue regeneration and exudate management. The fluid transport study shows that the resulting foams are capable of absorbing and transferring moisture from wounds. The foams exhibited significant liquid absorbency, with CH50BGF exhibiting the highest absorbency, reaching approximately 160% after 24 h. This enhanced absorption is attributed to the porous structure and chemical composition of the foams, particularly the presence of BG, which facilitates interactions with water molecules. Evaluation of WVT revealed that moistened specimens exhibited reduced WVT values compared to dry samples, indicating improved moisture retention capabilities under simulated wound conditions. The presence of BG in the composite foams contributed to higher WVT values, suggesting enhanced moisture management properties compared to pure CH foam. CH50BGF displayed higher absorbency values comparable to commercial dressings, indicating its potential for managing exuding wounds effectively. Cytotoxicity assays and histological staining confirmed the non-toxic nature of the foams to L-929 mammalian fibroblast cells. While reduced cell viability was observed for CHF compared to BG-containing samples, all samples were deemed non-toxic. The potential effects of BGs on cell adhesion and proliferation were noted, suggesting their role in promoting skin regeneration and wound healing processes. In summary, the foam dressings developed exhibit promising structural, fluid handling, moisture management, and biocompatibility profiles that make them suitable candidates for the treatment of highly exuding wounds such as full-thickness burns and pressure ulcers.

5. Acknowledgments

The authors thank CNPq (304415/2021-9), FAPEMIG (BPD-00883-22), and CAPES (PROEX) for their financial support of this project. Special thanks are also due to Prof. Dagoberto Brandão and Patricia Trigueiro for their contributions to the SEM analysis.

6. References

• ¹ Low ZWK, Li Z, Owh C, Chee PL, Ye E, Dan K, et al. Recent innovations in artificial skin. Biomater Sci. 2020;8(3):776-97. http://doi.org/10.1039/C9BM01445D
  » http://doi.org/10.1039/C9BM01445D
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Publication Dates

• Publication in this collection
  02 May 2025
• Date of issue
  2025

History

• Received
  12 Aug 2024
• Reviewed
  11 Nov 2024
• Accepted
  21 Dec 2024