**1. Introduction**

Wound healing is a complex, systemic, and regulated process to maintain human body functions. In wound healing, the major problem would be wound infections, which impair the healing process. As an act of prevention of this problem, antibiotic medications are prescribed to patients. However, this is ineffective in long-term treatments, especially for chronic wound patients, as this will cause multiresistant bacteria emergence. Therefore, in modern-day wound care, the functionality of wound dressings must be enhanced and addressed to properly manage and care for the wound as it may severely threaten an individual's quality of life and health.

Cotton fiber is the most recognized natural fiber, which has been widely used in the textile industry. In the biomedical field, cotton fiber has been modified to have antimicrobial properties [1], water repellency [2], and other enhancements of mechanical properties to work efficiently as a wound dressing. Cotton threads have a high specific area, are adjustable in shape, and have high absorption capability, which is good to absorb exudate, reduce blood loss, and keep the wound area free from other debris [3,4]. A minor setback is when a cotton thread wound dressing dries up, it tends to stick to the wound area during the removal process [5]. The removal of the dressing might cause discomfort to patients, causing secondary damage to newly developed tissue, and requires a tedious cleaning process. Therefore, the cotton thread should be modified to have properties that permit

**Citation:** Khairunnisa-Atiqah, M.K.; Salleh, K.M.; Ainul Hafiza, A.H.; Nyak Mazlan, N.S.; Mostapha, M.; Zakaria, S. Impact of Drying Regimes and Different Coating Layers on Carboxymethyl Cellulose Cross-Linked with Citric Acid on Cotton Thread Fibers for Wound Dressing Modification. *Polymers* **2022**, *14*, 1217. https://doi.org/10.3390/ polym14061217

Academic Editors: Domenico Acierno and Antonella Patti

Received: 20 December 2021 Accepted: 14 March 2022 Published: 17 March 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

balanced and maintaining moisture at the wound site to prevent the dressing from adhering to the wound, reducing pain and discomfort, thus accelerating wound healing.

Carboxymethyl cellulose (CMC) is used in the biomedical and pharmacology fields as an enzyme immobilizer, absorbent, r wound healing, and drug delivery. CMC is biocompatible with other biomaterials. Hence, CMC-based biomaterials with antibacterial properties for wound healing and tissue engineering could be fabricated [6]. CMC-coated wound dressing is more flexible, absorbs exudate, retains moisture to boost angiogenesis and autolytic debridement [7], is nontoxic to humans, and is water soluble [8]. Salt CMC derivatives, such as sodium CMC (Na-CMC) and calcium CMC (Ca-CMC), are commonly used. Na-CMC has an excellent compatibility with human skin, which shows a high film-forming capability and is proven to effectively eliminate microbial growths from wound beds through microbe adhesion and promote wound healing [9]. It is due to Na-CMC substituted carboxylated group (-COO) in the backbone along its cellulose chain. Besides, Na-CMC has been used to fabricate cellulose-based coating through chemical crosslinking as it can form a cross-linked network through ionic bonding, hydrogen bonding, or polymer–polymer interaction [10]. With these advantages, CMC-based biomaterials are widely used in wound dressing applications [7] to prevent wound infections. As coating agent, CMC improve thread quality and mechanical strength [11]. However, CMC on its own has poor mechanical properties. Therefore, citric acid (CA) was used as a crosslinker in this study. CA is present in citrus fruit, such as lemons and oranges. This natural organic acid consists of three carboxylic groups. CA is used in food processing and is now known in the biomedical field for its excellent antimicrobial and antioxidant properties. CA is also beneficial in the pharmaceutical application as it is used in various applications, such as cross-linking, interaction between molecules, and coating agents [12].

Oven drying (OD) is a conventional technique used with a standard temperature–time combination [13]. It is considered convenient since it can accommodate a large number of samples and has relatively rapid and precise temperature control to reach the desired temperature. However, the drawback is that temperature variations might occur due to the samples' size, weight, and position in the oven, which affect the total removal of moisture from samples, the risk of losing volatile substances or compounds, and sample decomposition during the long drying process [14–16]. In addition, sample decomposition is undesirable in wound dressing materials as it may have an immense degradable effect on temperature-sensitive medicinal substances. A more time-saving method, such as an infrared (IR) dryer, is viewed as an alternative to overcome this problem. IR drying provides rapid heating and moisture removal. It serves many advantages, such as high energy efficiency, faster heat transfer rate, and maintaining high-quality products [17,18]. During the drying process, the IR wavelength radiation emitted from the heat source passes through the wet sample and increases the temperature internally without heating the surrounding air [15]. The IR penetration causes water molecules to vibrate, which leads to heating [19]. The heat provided by IR interacts with the samples' internal structure and facilitates heating from the inner to the outer layer through the radiation and convection thermal phenomena, causing a decrease in moisture content through the evaporation process [19,20]. IR has been shown to provide more advantages in the drying method because it provides uniform heating, has a higher heat transfer rate, reduces processing time and energy, and improves the material quality [15,20]. Table 1 shows a comparison between IR drying and other drying techniques based on the cost-effectiveness, drying time, product quality, and advantages and disadvantages of the drying techniques. Therefore, a distinct comparison between oven and IR drying and a combination of both with regard to the quality of cotton thread wound dressing will be measured.



Our study aims to evaluate the effect of drying methods to CMC cross-linked with CA on cotton thread fibers' mechanical strength and its wettability properties for wound dressing enhancement. To achieve this aim, we investigate how different coating layers of CMC cross-linked with CA onto cotton thread fibers are influenced by different drying regimes. Our experimental approach evaluated whether drying regimes and two different applied coating layers can potentially affect the cotton thread absorption capability, surface morphology, and mechanical properties. The coated cotton thread moisture content and water absorption were determined. The CMC-coated cotton thread surface was visualized using an optical microscope (OM), and the mechanical properties, such as tensile strength, were assessed. Our results stipulate that a single-layer coat of CMC cross-linked with CA coated cotton thread undergoing IR drying shows better property enhancement of the cotton thread fibers than the oven or oven + IR drying method.

#### **2. Materials and Methods**

#### *2.1. Raw Materials*

Mercerized cotton thread (3-ply with 100% cotton) was purchased from Coats Cotton (Hungary, Europe). Solid powder sodium carboxymethyl cellulose (Na-CMC) (CAT. NO: 419273) with medium viscosity and a degree of substitution of 0.65–0.90 and citric acid (anhydrous, M*w*: 192.12) (CAS. NO: 77-92-9) were purchased from Sigma-Aldrich (St. Louis, MO, USA).

#### *2.2. Preparation of CMC and Citric Acid Coating Solution*

About 2% (*w*/*v*) of CMC as a coating material was dissolved in distilled water (dH2O) by stirring with a magnetic stirrer, forming a homogeneous aqueous solution. Then 4M CA was dissolved in dH2O. The 2M and 3M CA were prepared by diluting 4M CA.

#### *2.3. Design of Coating Processes*

Cotton thread fibers were washed before coating with 2% detergent solution and 80% ethanol and were oven-dried at 60 ◦C for 15 min. The coating process was based on previously published results [22] with modifications. The 2% CMC was prepared and allocated in 25 mL syringes with a 20-gauge needle size. Cotton thread fibers were soaked in the syringes with CMC solution for 18 h.

After the threads were soaked, the threads were pulled out from the syringe and were immediately submerged into beakers containing heated 2M, 3M, and 4M CA. The threads were left immersed for 1 h at 90 ◦C with constant stirring to promote CA and CMC interaction [23,24]. After the immersion, the excess CA was removed using filtered paper, and the thread groups were separately dried using OD and IR drying techniques at 65 ◦C for 30 min. In addition to that, OD drying was conducted in a convection oven (Memmert UFTS, Germany). For IR drying, the distance between the IR lamp and the sample in the drying machine was fixed at 7 cm (Desktop Infrared Drying Machine (GW-200H), Hoystar®, Guandong, China). During the sequential drying regime (OIR), drying was first conducted in the oven at 65 ◦C for 15 min, followed by IR drying for another 15 min, similarly at 65 ◦C, making a total drying time of 30 min.

The coating process was altered in six samples, which were divided into three sets. The first three sample groups were set as control, where no coating of CMC and CA was be performed. The second set consisted of the sample groups where one layer of CMC was performed. The third set is where two CMC layers were applied under the same conditions, with respective drying regimes after each coat. Once all samples were dried, the dry coat weight was measured as a control sample by weighing. Table 2 lists the coating parameters used to design the coating process.


**Table 2.** Design of coating trial with a defined number of layers and drying regimes. Trials with one layer of CMC are indicated by OD-1, IR-1, and OIR-1, while trials with two CMC layers are indicated by OD-2, IR-2, and OIR-2. CT-A, CT-B, and CT-C are the uncoated samples.

#### *2.4. Determination of Physical Characteristic of Uncoated and Coated Cotton Threads*

Basic physical properties, such as basis weight, thickness, and moisture content, were assessed using uncoated and CMC-coated samples. The basis weight of uncoated and coated samples was determined using an analytical balance (A&D Compact Analytical Balance, HR-250AZ), and the sample thickness was measured with an ABS Digital Thickness Gauge (Code: 547-301) (Mitutoyo, Kanagawa, Japan). After samples were dried according to the regimes, samples' moisture content was evaluated using a moisture analyzer machine (A&D Moisture Analyzer, MX-50).

#### *2.5. Evaluation of Mechanical Properties*

Tensile strength (TS), modulus, and percent elongation at break were measured using the Servo Control System Desktop Tensile Strength Tester AI-3000N (Qingdao, China). The test was performed based on the ASTM D3822 standard (Standard Test Method for Tensile Properties of Single Textile Fibers). Before running the tensile test, all samples were conditioned overnight in a drying cabinet at room temperature and 59.4% relative humidity (Weifo, Taiwan). The distance between the two clamps was set to 50 mm, and the strain rate speed was constant for all samples at 10 mm/min with a 10 kg load cell. The samples were cut at a length of 70 mm. Both coated and uncoated thread samples were secured with masking tape at both ends and inserted between the clamps to avoid fiber slipping during testing. The average fibers' strength and percent elongation were calculated based on five measurements. The tensile strength was obtained by dividing the average tensile load and average fiber diameter.
