Advantages and Prospective Implications of Smart Materials in Tissue Engineering: Piezoelectric, Shape Memory, and Hydrogels.

Conventional biomaterial is frequently used in the biomedical sector for various therapies, imaging, treatment, and theranostic functions. However, their properties are fixed to meet certain applications. Smart materials respond in a controllable and reversible way, modifying some of their properties because of external stimuli. However, protein-based smart materials allow modular protein domains with different functionalities and responsive behaviours to be easily combined. Wherein, these "smart" behaviours can be tuned by amino acid identity and sequence. This review aims to give an insight into the design of smart materials, mainly protein-based piezoelectric materials, shape-memory materials, and hydrogels, as well as highlight the current progress and challenges of protein-based smart materials in tissue engineering. These materials have demonstrated outstanding regeneration of neural, skin, cartilage, bone, and cardiac tissues with great stimuli-responsive properties, biocompatibility, biodegradability, and biofunctionality.

The degradation of single-use plastics and commercially viable bioplastics in the environment: A review.

Plastics have become an integral part of human life. Single-use plastics (SUPs) are disposable plastics designed to be used once then promptly discarded or recycled. This SUPs range from packaging and takeaway containers to disposable razors and hotel toiletries. Synthetic plastics, which are made of non-renewable petroleum and natural gas resources, require decades to perpetually disintegrate in nature thus contribute to plastic pollution worldwide, especially in marine environments. In response to these problems, bioplastics or bio-based and biodegradable polymers from renewable sources has been considered as an alternative. Understanding the mechanisms behind the degradation of conventional SUPs and biodegradability of their greener counterpart, bioplastics, is crucial for appropriate material selection in the future. This review aims to provide insights into the degradation or disintegration of conventional single-use plastics and the biodegradability of the different types of greener-counterparts, bioplastics, their mechanisms, and conditions. This review highlights on the biodegradation in the environments including composting systems. Here, the various types of alternative biodegradable polymers, such as bacterially biosynthesised bioplastics, natural fibre-reinforced plastics, starch-, cellulose-, lignin-, and soy-based polymers were explored. Review of past literature revealed that although bioplastics are relatively eco-friendly, their natural compositions and properties are inconsistent. Furthermore, the global plastic market for biodegradable plastics remains relatively small and require further research and commercialization efforts, especially considering the urgency of plastic and microplastic pollution as currently critical global issue. Biodegradable plastics have potential to replace conventional plastics as they show biodegradation ability under real environments, and thus intensive research on the various biodegradable plastics is needed to inform stakeholders and policy makers on the appropriate response to the gradually emerging biodegradable plastics.

Microneedles for Efficient and Precise Drug Delivery in Cancer Therapy.

Cancer is the leading cause of death, acting as a global burden, severely impacting the patients' quality of life and affecting the world economy despite the expansion of cumulative advances in oncology. The current conventional therapies for cancer which involve long treatment duration and systemic exposure of drugs leads to premature degradation of drugs, a massive amount of pain, side effects, as well as the recurrence of the condition. There is also an urgent demand for personalized and precision-based medicine, especially after the recent pandemic, to avoid future delays in diagnosis or treatments for cancer patients as they are very essential in reducing the global mortality rate. Recently, microneedles which consist of a patch with tiny, micron-sized needles attached to it have been quite a sensation as an emerging technology for transdermal application to diagnose or treat various illnesses. The application of microneedles in cancer therapies is also being extensively studied as they offer a myriad of benefits, especially since microneedle patches offer a better treatment approach through self administration, painless treatment, and being an economically and environmentally friendly approach in comparison with other conventional methods. The painless gains from microneedles significantly improves the survival rate of cancer patients. The emergence of versatile and innovative transdermal drug delivery systems presents a prime breakthrough opportunity for safer and more effective therapies, which could meet the demands of cancer diagnosis and treatment through different application scenarios. This review highlights the types of microneedles, fabrication methods and materials, along with the recent advances and opportunities. In addition, this review also addresses the challenges and limitations of microneedles in cancer therapy with solutions through current studies and future works to facilitate the clinical translation of microneedles in cancer therapies.

Polyhydroxyalkanoate (PHA) Biopolymer Synthesis by Marine Bacteria of the Malaysian Coral Triangle Region and Mining for PHA Synthase Genes.

Polyhydroxyalkanoate (PHA), a biodegradable and plastic-like biopolymer, has been receiving research and industrial attention due to severe plastic pollution, resource depletion, and global waste issues. This has spurred the isolation and characterisation of novel PHA-producing strains through cultivation and non-cultivation approaches, with a particular interest in genes encoding PHA synthesis pathways. Since sea sponges and sediment are marine benthic habitats known to be rich in microbial diversity, sponge tissues (Xestospongia muta and Aaptos aaptos) and sediment samples were collected in this study from Redang and Bidong islands located in the Malaysian Coral Triangle region. PHA synthase (phaC) genes were identified from sediment-associated bacterial strains using a cultivation approach and from sponge-associated bacterial metagenomes using a non-cultivation approach. In addition, phylogenetic diversity profiling was performed for the sponge-associated bacterial community using 16S ribosomal ribonucleic acid (16S rRNA) amplicon sequencing to screen for the potential presence of PHA-producer taxa. A total of three phaC genes from the bacterial metagenome of Aaptos and three phaC genes from sediment isolates (Sphingobacterium mizutaii UMTKB-6, Alcaligenes faecalis UMTKB-7, Acinetobacter calcoaceticus UMTKB-8) were identified. Produced PHA polymers were shown to be composed of 5C to nC monomers, with previously unreported PHA-producing ability of the S. mizutaii strain, as well as a 3-hydroxyvalerate-synthesising ability without precursor addition by the A. calcoaceticus strain.

Leveraging blockchain concepts as watermarkers of plastics for sustainable waste management in progressing circular economy.

Blockchain-integrated waste management and circular economy are emergent concepts that target minimising waste generation and fluctuations of resource commodity. Blockchain can support a circular economy and green principles by enabling information transparency, reliability and automation. Redesigning plastics by molecular tagging is the way forward to ensure synthetic plastics are kept in an infinite loop and support closed-loop recycling. The involvement of major corporations in product development and blockchain-integrated closed-loop recycling has resulted in several successful green chemical approaches toward circular plastic economy projects. Government policies and legislations are progressively supporting plastic redesigning for improving the plastic circular economy. Nevertheless, a systematic approach is required in addressing blockchain technology and plastic redesigning to effectively leverage circular economy initiatives.

Surface Modification of Sponge-like Porous Poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/Gelatine Blend Scaffolds for Potential Biomedical Applications.

In this study, we described the preparation of sponge-like porous scaffolds that are feasible for medical applications. A porous structure provides a good microenvironment for cell attachment and proliferation. In this study, a biocompatible PHA, poly(3-hydroxybutyrate-co-4-hydroxybutyrate) was blended with gelatine to improve the copolymer's hydrophilicity, while structural porosity was introduced into the scaffold via a combination of solvent casting and freeze-drying techniques. Scanning electron microscopy results revealed that the blended scaffolds exhibited higher porosity when the 4HB compositions of P(3HB-co-4HB) ranged from 27 mol% to 50 mol%, but porosity decreased with a high 4HB monomer composition of 82 mol%. The pore size, water absorption capacity, and cell proliferation assay results showed significant improvement after the final weight of blend scaffolds was reduced by half from the initial 0.79 g to 0.4 g. The pore size of 0.79g-(P27mol%G10) increased three-fold while the water absorption capacity of 0.4g-(P50mol%G10) increased to 325%. Meanwhile, the cell proliferation and attachment of 0.4g-(P50mol%G10) and 0.4g-(P82mol%G7.5) increased as compared to the initial seeding number. Based on the overall data obtained, we can conclude that the introduction of a small amount of gelatine into P(3HB-co-4HB) improved the physical and biological properties of blend scaffolds, and the 0.4g-(P50mol%G10) shows great potential for medical applications considering its unique structure and properties.

Surface Characterization and Physiochemical Evaluation of P(3HB-co-4HB)-Collagen Peptide Scaffolds with Silver Sulfadiazine as Antimicrobial Agent for Potential Infection-Resistance Biomaterial.

Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] is a bacterial derived biopolymer widely known for its unique physical and mechanical properties to be used in biomedical application. In this study, antimicrobial agent silver sulfadiazine (SSD) coat/collagen peptide coat-P(3HB-co-4HB) (SCCC) and SSD blend/collagen peptide coat-P(3HB-co-4HB) scaffolds (SBCC) were fabricated using a green salt leaching technique combined with freeze-drying. This was then followed by the incorporation of collagen peptides at various concentrations (2.5-12.5 wt.%) to P(3HB-co-4HB) using collagen-coating. As a result, two types of P(3HB-co-4HB) scaffolds were fabricated, including SCCC and SBCC scaffolds. The increasing concentrations of collagen peptides from 2.5 wt.% to 12.5 wt.% exhibited a decline in their porosity. The wettability and hydrophilicity increased as the concentration of collagen peptides in the scaffolds increased. In terms of the cytotoxic results, MTS assay demonstrated the L929 fibroblast scaffolds adhered well to the fabricated scaffolds. The 10 wt.% collagen peptides coated SCCC and SBCC scaffolds displayed highest cell proliferation rate. The antimicrobial analysis of the fabricated scaffolds exhibited 100% inhibition towards various pathogenic microorganisms. However, the SCCC scaffold exhibited 100% inhibition between 12 and 24 h, but the SBCC scaffolds with SSD impregnated in the scaffold had controlled release of the antimicrobial agent. Thus, this study will elucidate the surface interface-cell interactions of the SSD-P(3HB-co-4HB)-collagen peptide scaffolds and controlled release of SSD, antimicrobial agent.

Recent Advances in the Biosynthesis of Polyhydroxyalkanoates from Lignocellulosic Feedstocks.

Polyhydroxyalkanoates (PHA) are biodegradable polymers that are considered able to replace synthetic plastic because their biochemical characteristics are in some cases the same as other biodegradable polymers. However, due to the disadvantages of costly and non-renewable carbon sources, the production of PHA has been lower in the industrial sector against conventional plastics. At the same time, first-generation sugar-based cultivated feedstocks as substrates for PHA production threatens food security and considerably require other resources such as land and energy. Therefore, attempts have been made in pursuit of suitable sustainable and affordable sources of carbon to reduce production costs. Thus, in this review, we highlight utilising waste lignocellulosic feedstocks (LF) as a renewable and inexpensive carbon source to produce PHA. These waste feedstocks, second-generation plant lignocellulosic biomass, such as maize stoves, dedicated energy crops, rice straws, wood chips, are commonly available renewable biomass sources with a steady supply of about 150 billion tonnes per year of global yield. The generation of PHA from lignocellulose is still in its infancy, hence more screening of lignocellulosic materials and improvements in downstream processing and substrate pre-treatment are needed in the future to further advance the biopolymer sector.

Transformation of Biowaste for Medical Applications: Incorporation of Biologically Derived Silver Nanoparticles as Antimicrobial Coating.

Nanobiotechnology has undoubtedly influenced major breakthroughs in medical sciences. Application of nanosized materials has made it possible for researchers to investigate a broad spectrum of treatments for diseases with minimally invasive procedures. Silver nanoparticles (AgNPs) have been a subject of investigation for numerous applications in agriculture, water treatment, biosensors, textiles, and the food industry as well as in the medical field, mainly due to their antimicrobial properties and nanoparticle nature. In general, AgNPs are known for their superior physical, chemical, and biological properties. The properties of AgNPs differ based on their methods of synthesis and to date, the biological method has been preferred because it is rapid, nontoxic, and can produce well-defined size and morphology under optimized conditions. Nevertheless, the common issue concerning biological or biobased production is its sustainability. Researchers have employed various strategies in addressing this shortcoming, such as recently testing agricultural biowastes such as fruit peels for the synthesis of AgNPs. The use of biowastes is definitely cost-effective and eco-friendly; moreover, it has been reported that the reduction process is simple and rapid with reasonably high yield. This review aims to address the developments in using fruit- and vegetable-based biowastes for biologically producing AgNPs to be applied as antimicrobial coatings in biomedical applications.

Bioconversion of agro-industry sourced biowaste into biomaterials via microbial factories - A viable domain of circular economy.

Global increase in demand for food supply has resulted in surplus generation of wastes. What was once considered wastes, has now become a resource. Studies were carried out on the conversion of biowastes into wealth using methods such as extraction, incineration and microbial intervention. Agro-industry biowastes are promising sources of carbon for microbial fermentation to be transformed into value-added products. In the era of circular economy, the goal is to establish an economic system which aims to eliminate waste and ensure continual use of resources in a close-loop cycle. Biowaste collection is technically and economically practicable, hence it serves as a renewable carbon feedstock. Biowastes are commonly biotransformed into value-added materials such as bioethanol, bioplastics, biofuels, biohydrogen, biobutanol and biogas. This review reveals the recent developments on microbial transformation of biowastes into biotechnologically important products. This approach addresses measures taken globally to valorize waste to achieve low carbon economy. The sustainable use of these renewable resources is a positive approach towards waste management and promoting circular economy.

Elucidation of Antimicrobial Silver Sulfadiazine (SSD) Blend/Poly(3-Hydroxybutyrate-co-4-Hydroxybutyrate) Immobilised with Collagen Peptide as Potential Biomaterial.

The quest for a suitable biomaterial for medical application and tissue regeneration has resulted in the extensive research of surface functionalization of material. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] is a bacterial polymer well-known for its high levels of biocompatibility, non-genotoxicity, and minimal tissue response. We have designed a porous antimicrobial silver SSD blend/poly(3HB-co-4HB)-collagen peptide scaffold using a combination of simple techniques to develop a scaffold with an inter-connected microporous pore in this study. The collagen peptide was immobilised via -NH2 group via aminolysis. In order to improve the antimicrobial performance of the scaffold, silver sulfadiazine (SSD) was impregnated in the scaffolds. To confirm the immobilised collagen peptide and SSD, the scaffold was characterized using FTIR. Herein, based on the cell proliferation assay of the L929 fibroblast cells, enhanced bioactivity of the scaffold with improved wettability facilitated increased cell proliferation. The antimicrobial activity of the SSD blend/P(3HB-co-4HB)-collagen peptide in reference to the pathogenic Gram-negative, Gram-positive bacteria and yeast Candida albicans exhibited SSD blend/poly(3HB-co-4HB)-12.5 wt% collagen peptide as significant construct of biocompatible antibacterial biomaterials. Thus, SSD blend/P(3HB-co-4HB)-collagen peptide scaffold from this finding has high potential to be further developed as biomaterial.

Surface-Modified Highly Biocompatible Bacterial-poly(3-hydroxybutyrate-co-4-hydroxybutyrate): A Review on the Promising Next-Generation Biomaterial.

Polyhydroxyalkanoates (PHAs) are bacteria derived bio-based polymers that are synthesised under limited conditions of nutritional elements with excess carbon sources. Among the members of PHAs, poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [(P(3HB-co-4HB)] emerges as an attractive biomaterial to be applied in medical applications owing to its desirable mechanical and physical properties, non-genotoxicity and biocompatibility eliciting appropriate host tissue responses. The tailorable physical and chemical properties and easy surface functionalisation of P(3HB-co-4HB) increase its practicality to be developed as functional medical substitutes. However, its applicability is sometimes limited due to its hydrophobic nature due to fewer bio-recognition sites. In this review, we demonstrate how surface modifications of PHAs, mainly P(3HB-co-4HB), will overcome these limitations and facilitate their use in diverse medical applications. The integration of nanotechnology has drastically enhanced the functionality of P(3HB-co-4HB) biomaterials for application in complex biological environments of the human body. The design of versatile P(3HB-co-4HB) materials with surface modifications promise a non-cytotoxic and biocompatible material without inducing severe inflammatory responses for enhanced effective alternatives in healthcare biotechnology. The enticing work carried out with P(3HB-co-4HB) promises to be one of the next-generation materials in biomedicines which will facilitate translation into the clinic in the future.

Elucidating the Surface Functionality of Biomimetic RGD Peptides Immobilized on Nano-P(3HB-co-4HB) for H9c2 Myoblast Cell Proliferation.

Biomaterial scaffolds play crucial role to promote cell proliferation and foster the regeneration of new tissues. The progress in material science has paved the way for the generation of ingenious biomaterials. However, these biomaterials require further optimization to be effectively used in existing clinical treatments. It is crucial to develop biomaterials which mimics structure that can be actively involved in delivering signals to cells for the formation of the regenerated tissue. In this research we nanoengineered a functional scaffold to support the proliferation of myoblast cells. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] copolymer is chosen as scaffold material owing to its desirable mechanical and physical properties combined with good biocompatibility, thus eliciting appropriate host tissue responses. In this study P(3HB-co-4HB) copolymer was biosynthesized using Cupriavidus malaysiensis USMAA1020 transformant harboring additional PHA synthase gene, and the viability of a novel P(3HB-co-4HB) electrospun nanofiber scaffold, surface functionalized with RGD peptides, was explored. In order to immobilize RGD peptides molecules onto the P(3HB-co-4HB) nanofibers surface, an aminolysis reaction was performed. The nanoengineered scaffolds were characterized using SEM, organic elemental analysis (CHN analysis), FTIR, surface wettability and their in vitro degradation behavior was evaluated. The cell culture study using H9c2 myoblast cells was conducted to assess the in vitro cellular response of the engineered scaffold. Our results demonstrated that nano-P(3HB-co-4HB)-RGD scaffold possessed an average fiber diameter distribution between 200 and 300 nm, closely biomimicking, from a morphological point of view, the structural ECM components, thus acting as potential ECM analogs. This study indicates that the surface conjugation of biomimetic RGD peptide to the nano-P(3HB-co-4HB) fibers increased the surface wettability (15 ± 2°) and enhanced H9c2 myoblast cells attachment and proliferation. In summary, the study reveals that nano-P(3HB-co-4HB)-RGD scaffold can be considered a promising candidate to be further explored as cardiac construct for building cardiac construct.

En route to economical eco-friendly solvent system in enhancing sustainable recovery of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymer.

Separation of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] from bacterial cell matter is a critical step in the downstream process with respect to material quality and eco-balance as P(3HB-co-4HB) is widely used for biomedical applications. Therefore, an efficient and eco-based extraction of P(3HB-co-4HB) using a combination of NaOH and Lysol in digesting the non-polymeric cell material (NPCM) digestion is developed. The NaOH and Lysol show synergistic influence on the copolymer extraction at a high purity and recovery of 97 and 98 wt% respectively. The optimized cell digestion method was found applicable to a vast batch of cells containing copolymers from various 4HB monomer compositions. At the largest extraction volume of 100 L, P(3HB-co-4HB) with a purity of 89 wt% was extracted with a maximum recovery of 90 wt%. The method developed has also eliminated the cell pretreatment step. The extraction method developed in this research has not only produced an economic and efficient copolymer recovery but has also retained the copolymer quality, in term of its molecular weight and thermal properties. It demonstrates a practical and promising downstream processing method in recovering the copolymer effectively from the bacterial biomass.