1. Introduction: Environmental Impact of Plastic
The exponential increase in global plastic consumption since its discovery in the 20th century has led to plastics becoming an essential part of our daily lives. Their versatility, lightweight, durability, and ease of production have established their widespread use. From the 1950s to 2019, the industry produced approximately 9200 million metric tons (Mt) of plastic. Currently, it is estimated that about 2500 Mt of this plastic remains in active use, representing 30% of all plastics ever produced. In contrast, the remaining 70% is classified as waste, which contributes to significant environmental contamination, as highlighted by recent studies
[1].
A primary concern with plastic pollution is its high durability. Studies indicate that, depending on the material structure and environmental conditions, plastics can persist for hundreds of years
[2]. For example, research by Chamas et al.
[3] found that high-density polyethylene (HDPE) bottles can take around 58 years to decompose in marine environments, and HDPE pipes may persist for as long as 1200 years. This results in a significant accumulation of plastic materials on both land and sea, causing serious ecological damage. This concerning situation highlights the urgent need for sustainable, non-toxic, and biodegradable alternatives to conventional plastics
[4][5][6]. In this context, bio-derived polymers like polyhydroxyalkanoates (PHAs) are gaining attention as promising and environmentally friendly alternatives
[7].
1.1. Polyhydroxyalkanoates (PHAs): Biodegradable Alternative to Conventional Plastics
Polyhydroxyalkanoates (PHAs) are natural polyesters produced by a wide range of bacterial microorganisms
[8]. These bacteria can accumulate PHAs as energy storage compounds within their cells. PHAs share similar physicochemical properties with conventional plastics such as polypropylene (PP) and polyethylene (PE)
[9]. However, in terms of biodegradability, PHAs are considered 100% biodegradable materials that meet almost all established standards for biodegradation in various environments. Compared to other common biodegradable bioplastics like polylactic acid (PLA), PHAs do not require any specific conditions such as controlled temperatures or specific pH levels for complete degradation
[8]. Furthermore, PHAs are among the few biopolymers known to degrade effectively not only in landfills but also in challenging marine and freshwater environments
[10], where degradation is typically more complex.
Beyond their environmental benefits, PHAs are also recognized for their biocompatibility and non-toxicity to humans
[11]. These unique properties make them highly suitable for designing tissue engineering applications. In fact, a significant amount of research on PHA applications has been focused on the biomedical field, especially in regenerative engineering applications like bone regeneration
[12][13][14]. Such research underscores the potential of PHAs to revolutionize both environmental sustainability and healthcare technologies.
To date, more than 150 different monomers have been identified within the PHA family
[15][16]. Based on the length of their carbon side chains, PHAs are systematically classified into short chain lengths (4 to 5 carbons) and medium chain lengths (6 to 12 carbons). Some studies have observed the presence of long-chain PHAs containing more than 14 carbon units; however, research on these PHAs is still limited
[17][18]. In addition to simple PHAs, copolymers consisting of two different monomers are also identified. Examples include poly(3-hydroxybutyrate-
co-3-hydroxyvalerate) (PHBV), poly(3-hydroxybutyrate-
co-4-hydroxybutyrate) (P3HB4HB), and poly(3-hydroxybutyrate-
co-hydroxyhexanoate) (PHBHHx)
[19][20][21]. These copolymers offer tunable properties, providing a variety of mechanical and thermal properties by altering the comonomer composition.
1.2. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)
Among the various biopolymers derived from the PHA family, the copolymer poly(3-hydroxybutyrate-
co-3-hydroxyvalerate), commonly known as PHBV, stands out for its inherent versatility. Unlike many other members of the PHA family that are derived from a single monomer and exhibit consistent physicochemical properties, PHBV offers the unique advantage of tunability. By adjusting the ratio of 3HB to 3HV monomers, the material properties can be tailored to produce products from flexible films to rigid molded objects
[11]. This adaptability made PHBV more versatile and expanded its potential applications
[22]. As a result, PHBV quickly attracted significant commercial interest. Companies began to explore their potential to produce biodegradable plastics on a commercial scale, providing an alternative material to traditional plastics.
2. Applications of PHBV-Based Materials
PHBV has emerged as a promising biopolymer due to its unique combination of biodegradability and versatile material properties.
2.1. Medical Sector
2.1.1. Tissue Engineering
Tissue engineering commonly includes tissue regeneration, which needs an environment with robust mechanical properties to facilitate the rapid growth of tissue cells. Consequently, scaffolds used for tissue engineering must be biocompatible, sterilized, and capable of maintaining mechanical integrity. Among the available biomaterials, PHA-based polymers are widely implicated due to their pronounced biocompatibility. These polymers are extensively used for bone tissue engineering but are also applied to urethral reconstructions and in the treatment of wounds using absorbable sutures
[23].
In recent studies, Xue and colleagues
[24] explored the feasibility of combining cartilage progenitor cells (CPCs) with PHBV to produce tissue-engineered cartilages. Their findings indicated that CPC-PHBV constructs were transformed into ivory-whitish, cartilage-like tissue after 6 weeks of subcutaneous implantation in nude mice. Histological examinations revealed the presence of numerous typical cartilaginous structures in the chondrocyte group and some in the CPC group, but none in the BMSC (bone marrow-derived stem cells) group. The results showed the potential of using PHBV materials in combination with CPCs to develop tissue-engineered cartilage
[24].
2.1.2. Drug Delivery
Drug delivery technology plays an important role in improving human health. Traditional drug delivery is limited in practical applications due to factors such as toxicity, uncertainty, and lack of selectivity. However, the use of PHA as a material for drug carriers can potentially overcome some of these limitations. PHA-based drug carriers exhibit biocompatibility and biodegradability, which significantly reduce toxicity problems associated with traditional drug delivery systems.
The research developed by Cabaña-Brunod et al.
[25] has found that PHBV nanoparticles (NPs) could be effectively used as a delivery system for iE-DAP, a NOD1 (intracellular receptor) agonist. The NPs showed controlled release of iE-DAP in-vitro, and the response of the encapsulated agonist was found to be higher than its free form. This feature highlighted that PHBV NPs can activate intracellular receptors, triggering an immune response through the release of the NOD1 agonist, iE-DAP.
Furthermore, PHA-based drug carriers can be functionalized with various ligands for the specific treatment of different diseases. In recent studies, Alp et al.
[26] developed PHBV nanoparticles for targeted delivery of etoposide drugs to osteosarcoma cells, using folic acid as a targeting ligand to exploit folate receptor-mediated endocytosis. The findings suggest that PHBV nanoparticles loaded with etoposide and functionalized with folic acid can potentially be used for the targeted treatment of osteosarcoma.
One of the most promising advantages of PHBV in drug delivery systems is its ability to sustain drug release. This ensures that therapeutic levels are consistently maintained over a specified period, which is often a challenge in drug delivery system design. In a study by Yingjun Wang et al.
[27], PHBV/HA (hydroxyapatite) composite microspheres were developed to regulate the release rate of the antibiotic gentamicin, which served as a model drug. These microspheres were created using an S/O/W (solid-in-oil-in-water) emulsion solvent evaporation method. Surprisingly, they showed an exceptionally low initial burst release of the drug. This minimal release can be attributed to the high affinity and absorbability of nano-HA particles. The sustained release of the drug lasted for more than 10 weeks. This could be particularly beneficial in applications where consistent drug release is needed over a prolonged period, such as in antibiotic therapy, to avoid frequent dosing and improve patient compliance.
2.2. Food Packaging
The extensive use of conventional plastic packaging has led to critical environmental problems, including widespread plastic pollution and waste accumulation. There is a need to look for alternative materials. PHBV emerges as a promising option, as it is a bio-based and biodegradable polymer that mitigates environmental impact, ensures consumer safety, and provides effective food preservation.
Ferri et al.
[28] integrated PHBV with tannins to develop a fully biobased and biodegradable material suitable for food packaging. This innovative material not only reduces the environmental impact of fossil-based plastics but also introduces functionalities that extend the shelf life of food and inform consumers about its quality and freshness. The researchers prepared PHBV/tannin films using the solvent casting method. The resulting films exhibited antioxidant, UV protection, and gas barrier properties. The films were found to be suitable for temperatures ranging from refrigeration levels to those required for heating food (up to 200 °C). In terms of tensile strength, they were comparable to conventional polymers and biopolymers used in packaging. Interestingly, the PHBV/tannin films also demonstrated the ability to calorimetrically detect ammonia vapors, suggesting potential applicability as a smart indicator of food spoilage. The authors suggested that tannins could add multifunctional properties to a polymeric material, providing an attractive alternative to petroleum-based plastics for smart food packaging applications.
Bonnenfant, Gontard, and Aouf
[29] evaluated the safety and structural integrity of PHBV under different reuse conditions, including food contact, washing, and subsequent food contact. Valuable insights were provided into the potential of these biodegradable polymers for sustainable food packaging solutions. Their study revealed that PHBV exhibits an overall migration close to zero in a complete reuse cycle with certain food simulants, demonstrating its potential safety in reuse applications.
2.3. Agriculture
Mulch films play a pivotal role in modern agriculture, which offer numerous benefits, such as improving the overall productivity and the quality of crop production. However, traditional mulch films are often made of non-degradable plastics, which pose significant environmental challenges
[30]. These films can cause soil pollution, disrupt ecosystems, and contribute to global plastic waste
[31]. Tian et al.
[32] provided a comprehensive review of the application of PHA in the development of biodegradable mulch films. The urgency and importance of this development was highlighted. The review analyzed the feasibility of using PHA as an alternative material and emphasized the challenges faced in its production, such as its proneness to thermal degradation during film extrusion. Various strategies, such as blending with other polymers and structural design, were explored to enhance the thermal and mechanical performance of PHA.
Despite the potential of PHAs in the agricultural sector, a study by Liu et al.
[33] highlighted significant obstacles to their widespread adoption of mulch films. These challenges include the high production cost of PHAs, their limited availability, and the need for further research to improve their mechanical and physical properties to meet the diverse demands of agricultural applications. Additionally, the authors emphasized the need to develop standards and guidelines for biodegradable mulch films to ensure their safe and effective use in agriculture.
Intriguingly, a recent study conducted by Brown et al.
[34] demonstrated that even at minimal levels of contamination, PHBV microplastics in soil could negatively affect both plant and soil health. This contamination could reduce plant growth, modify lead metabolic functions, and affect soil microbial activity and community composition. These findings reflect Liu’s concerns, emphasizing the need for caution and more research into the use of biodegradable materials in agriculture, especially when these materials can interact with soil and plants.
2.4. Three-Dimensional Printing
The use of PHBV in 3D printing applications has advanced significantly in recent years, driven by the material’s biodegradability and biocompatibility. PHBV is often blended with other polymers, such as PLA, to enhance its thermal and mechanical properties, making it more suitable for 3D printing applications. Vigil Fuentes et al.
[35] used styrene–acrylate copolymers as chain extenders to improve the compatibility and thermal resistance of PHBV blends. They successfully demonstrated that the incorporation of a chain extender allowed for higher printing temperature and sufficient printing speed, thus enhancing 3D printability. The optimized printed samples exhibited higher storage modulus and strength, resulting in stiffer and stronger parts. This research not only paves the way for further exploration of the use of biodegradable polymers in 3D printing but also provides a framework for developing materials that can be used in various applications, such as biomedical devices and environmentally friendly consumer products.
The 3D-printed scaffolds of PHBV combined with calcium sulfate hemihydrate (CaSH) developed by Ye et al.
[36] is another example of 3D application. They used the fused deposition modeling (FDM) technique to fabricate scaffolds and subsequently coated them with chitosan (CS) acetic acid solution. Once dried and neutralized, a chitosan hydrogel formed on the scaffold surface. Their findings indicated that resulting PHBV/CaSH/CS scaffolds significantly promoted the adhesion and proliferation of rat bone marrow stromal cells (rBMSCs). Furthermore, these scaffolds showed a higher expression level of the osteogenic gene compared to PHBV and PHBV/CaSH scaffolds, which improved the osteogenesis of rBMSCs. In vivo experiments further corroborated these results and demonstrated that PHBV/CaSH/CS scaffolds effectively promoted new bone formation. This innovative integration of 3D-printed PHBV/CaSH scaffold and CS hydrogel offers a promising approach to enhance osteogenesis properties, presenting a potential solution to repair bone defects.
2.5. Textile Industry
The textile industry has been identified as a major polluter due to its dependence on petroleum-derived materials and the emission of harmful chemicals during production
[37]. The use of biodegradable materials such as PHBV is gaining a lot of attention as an eco-friendly alternative. Its ability to degrade more quickly minimizes long-term environmental waste. Within the textile sector, various applications of PHBV have been explored. For example, Huang et al.
[38] developed a multi-filament yarn using a PLA/PHBV blend. The resulting yarn exhibited thermal and mechanical properties suitable for standard textile and dyeing/finishing processes. Single-knit fabrics made from this PLA/PHBV filament yarn met industrial standards in terms of strength, stretch, and recovery. Furthermore, their study highlighted the excellent antibacterial performance of 100% PLA/PHBV fabrics against many microorganisms. A study conducted by Xu et al.
[39] also emphasized the antibacterial properties of PHBV materials, suggesting their potential to produce hygienic textile products without the need for synthetic chemical treatments. Furthermore, the integration of reinforcing agent, such as lignocellulosic fibers, has been developed to improve mechanical limitations such as brittleness and the high cost of PHBV materials, thus expanding their applicability in the textile sector
[40].