Controllable Biodegradability Research Articles

3D Breast Cancer Model on Silk Fibroin-Integrated Microfluidic Chips.

To imitate in vivo environment of cells, microfluidics offer controllable fashions at micro-scale and enable regulate flow-related parameters precisely, leveraging the current state of 3D systems to 4D level through the inclusion of flow and shear stress. In particular, integrating silk fibroin as an adhering layer with microfluidic chips enables to form more comprehensive and biocompatible network between cells since silk fibroin holds outstanding mechanical and biological properties such as easy processability, biocompatibility, controllable biodegradation, and versatile functionalization. In this chapter, we describe design and fabrication of a microfluidic chip, with silk fibroin-covered microchannels for the formation of 3D structures, such as MCF-7 (human breast cancer) cell spheroids as a model system. All the steps performed here are characterized by surface-sensitive tools and standard tissue culture methods. Overall, this strategy can be easily integrated into various high-tech application areas such as drug delivery systems, regenerative medicine, and tissue engineering in near future.

Development of citric acid-based biomaterials for biomedical applications.

The development of bioactive materials with controllable preparation is of great significance for biomedical engineering. Citric acid-based biomaterials are one of the few bioactive materials with many advantages such as simple synthesis, controllable structure, biocompatibility, biomimetic viscoelastic mechanical behavior, controllable biodegradability, and further functionalization. In this paper, we review the development of multifunctional citrate-based biomaterials for biomedical applications, and summarize their multifunctional properties in terms of physical, chemical, and biological aspects, and finally the applications of citrate-based biomaterials in biomedical engineering, including bone tissue engineering, skin tissue engineering, drug/cell delivery, vascular and neural tissue engineering, and bioimaging.

A Customizable Proteinic Bioadhesive Patch with Water-Switchable Underwater Adhesiveness, Adjustable Biodegradability, and Modifiable Stretchability for Healing Diverse Internal Wounds.

Customizable bioadhesives for individual organ requirements, including tissue type and motion, are essential, especially given the rise in implantable medical device applications demanding adequate underwater adhesion. While synthetic bioadhesives are widely used, their toxicity upon degradation shifts focus to biocompatible natural biomaterials. However, enhancing the adhesive strengths of these biomaterials presents ongoing challenges while accommodating the unique properties of specific organs. To address these issues, three types of customized underwater bioadhesive patches (CUBAPs) with strong, water-responsive adhesion and controllable biodegradability and stretchability based on bioengineered mussel adhesive proteins conjugated with acrylic acid and/or methacrylic acid are proposed. The CUBAP system, although initially nonadhesive, shows strong underwater adhesion upon hydration, adjustable biodegradation, and adequate physical properties by adjusting the ratio of poly(acrylic acid) and poly(methacrylic acid). Through ex vivo and in vivo evaluations using defective organs and the implantation of electronic devices, the suitability of using CUBAPs for effective wound healing in diverse internal organs is demonstrated. Thus, this innovative CUBAP system offers strong underwater adhesiveness with tailored biodegradation timing and physical properties, giving it great potential in various biomedical applications.

Novel Applications of Silk Proteins Based on Their Interactions with Metal Ions

Silk secreted by Bombyx mori L. silkworm has become one of the most important biomaterials, due to its excellent biocompatibility, controllable biodegradability, superior processability, and unique mechanical properties. Silk fibroin and sericin, as the two components of silk, contain abundant polar functional groups, and thus can bind metal ions through electrostatic interaction and chelation. Based on this binding, silk proteins not only can be used to fabricate ecofriendly and efficient adsorbents to remove heavy metals from waterbodies, but also can synthesize metal nanostructures (nanoparticles or nanoclusters) to form silk/metal composites with amazing optical or electrochemical characteristics. This binding also can be manipulated to optimize silk’s performance. This review focuses on discussing and summarizing advances in the use of silk fibroin and sericin for heavy metal ion-contaminated water remediation, biosensing materials, and electrochemical materials from the perspective of the interaction between silk proteins and metal ions. The performance enhancement of silk using metal ions is also analyzed. Moreover, the silk proteins’ interactions with metal ions and related structural features that contribute to the above sustainable applications are illustrated to lay a theoretical foundation. This review will favor the expansion of the applications of silk in both the traditional textile field and new biomaterials.

Programmable all-DNA hydrogels based on rolling circle and multiprimed chain amplification products.

Soft, biocompatible, and tunable materials offer biomedical engineers and material scientists programmable matrices for a variety of biomedical applications. In this regard, DNA hydrogels have emerged as highly promising biomaterials that offer programmable self-assembly, superior biocompatibility, and the presence of specific molecular identifiable structures. Many types of DNA hydrogels have been developed, yet the programmability of the DNA building blocks has not been fully exploited, and further efforts must be directed toward understanding how to finely tune their properties in a predictable manner. Herein, we develop physically crosslinked all-DNA hydrogels with tunable morphology and controllable biodegradation, based on rolling circle amplification and multiprimed chain amplification products. Through molecular engineering of the DNA sequences and their nano-/microscale architectures, the precursors self-assemble in a controlled manner to produce soft hydrogels in an efficient, cost-effective, and highly tunable manner. Notably, we develop a novel DNA microladder architecture that serves as a framework for modulating the hydrogel properties, including over an order of magnitude change in pore size and up to 50% change in biodegradation rate. Overall, we demonstrate how the properties of this DNA-based biomaterial can be tuned by modulating the amounts of rigid double-stranded DNA chains compared to flexible single-stranded DNA chains, as well as through the precursor architecture. Ultimately, this work opens new avenues for the development of programmable and biodegradable soft materials in which DNA functions not only as a store of genetic information but also as a versatile polymeric biomaterial and molecularly engineered macroscale scaffold.

Enhanced in-vitro biodegradation, bioactivity, and mechanical properties of Mg-based biocomposite via addition of calcium-silicate-based bioceramic through friction stir processing as resorbable temporary bone implant

Bioabsorbable Mg and alloys have been used as metallic biomaterials for orthopedic implant applications due to their similar mechanical properties to human natural bone. High biodegradation rate is the main reason for limiting clinical applications of Mg and alloys in biological media. In order to achieve long-lasting bio applications of bioabsorbable WE43 Mg alloy, it is necessary to improve strength and bioactivity and control biodegradation rate of this material. In this study, Mg-based biocomposites are produced using friction stir processing (FSP) by addition of wollastonite (CaSiO3) calcium-silicate-based bioactive reinforcing particle into Mg matrix. The results showed that applied severe plastic deformation during FSP caused formation of ultra-fine grain structure with homogenous distribution of secondary phase particles, which resulted in a remarkable improvement of ductility, strength and load bearing capacity of FSPed Mg matrix. Also, biodegradation behavior of resulting biocomposite was evaluated using electrochemical methods and in-vitro immersion test in simulated body fluid (SBF) and phosphate-buffered saline (PBS) at 37.5 °C. The results revealed that processed bioabsorbable Mg alloy showed a lower biodegradation rate compared to monolithic Mg alloy. Furthermore, the presence of wollastonite bioceramic particles significantly enhanced strength and reduced biodegradation of the Mg-based biocomposite. Moreover, the addition of wollastonite bioceramic particles positively affected the bioactivity of Mg matrix by forming a cauliflower shaped bone-like hydroxyapatite layer on the surface after 28 days of immersion in SBF and stimulate bone tissue regeneration.

Advanced Silk Fibroin Biomaterials-Based Microneedles for Healthcare.

Microneedles are a promising transdermal drug delivery system that has the advantages of minimal invasiveness, painlessness, and on-demand drug delivery compared with commonly used medical techniques. Natural resources are developed as next-generation materials for microneedles with varying degrees of success. Among them, silk fibroin is a natural polymer obtained from silkworms with good biocompatibility, high hardness, and controllable biodegradability. These properties provide many opportunities for integrating silk fibroin with implantable microneedle systems. In this review, we summarized the research progress of silk fibroin microneedles in recent years, including their materials, processing technology, detection, drug release methods, and applications. Besides, the research and development of silk fibroin in a multidimensional way are analyzed. Finally, we expect that silk fibroin microneedles will have excellent development prospects in various fields (Figure1). This article is protected by copyright. All rights reserved.

Review on Fabrication and Application of Regenerated Bombyx mori Silk Fibroin Materials

Abstract Natural silk fiber derived from the Bombyx mori (B. mori) silkworm has long been used as a luxury raw material in textile industry because of its shimmering appearance and durability, and as surgical suture for its high strength and flexibility. Regenerated silk fibroin, as the main protein extracted from the cocoons of the B. mori silkworm, recently has gained considerable attention due to its outstanding properties, including facile processability, superior biocompatibility, controllable biodegradation, and versatile functionalization. Tremendous effort has been made to fabricate silk fibroin into various promising materials with controlled structural and functional characteristics for advanced utilities in a multitude of biomedical applications, flexible optics, electronics devices, and filtration systems. Herein, reverse engineered silk fibroin extraction methods are reviewed, recent advances in extraction techniques are discussed. Fabrication methods of silk fibroin materials in various formats are also addressed in detail; in particular, progress in new fabrication technologies is presented. Attractive applications of silk fibroin-based materials are then summarized and highlighted. The challenges faced by current approaches in production of silk fibroin-based materials and future directions acquired for pushing these favorable materials further toward above mentioned applications are further elaborated.

Thermal Degradation Mechanism and Decomposition Kinetic Studies of Poly(Ethylene Succinate)/Hemp Fiber Composites

The continuous depletion of natural resources coupled with plastics pollution, has prompted the scientific community to explore alternative biobased and/or biodegradable polymers. Poly(ethylene succinate) (PESu) is a promising substitute due to its high processability and controllable biodegradation rate. Meanwhile, hemp possesses interesting properties such as being lightweight, exhibiting excellent long-term mechanical stability, and having low carbon emissions, making it an ideal option for wood replacement. Thus, PESu/hemp fiber composites (with and without compatibilizer) were prepared novel sustainable materials with improved properties. The present study aims to investigate the thermal degradation of PESu/hemp fiber composites. More specifically, thermogravimetric analysis (TGA) and pyrolysis-gas chromatography/mass spectrometry (Py–GC/MS) were employed to examine the degradation mechanism and identify decomposition products. The isoconversional methods of Vyazovkin and Friedman, as well as the model free methods, provided comparable results. Samples without compatibilizer were characterized by a two-step Cn autocatalytic mechanism, while those with compatibilizer showed a triple Cn mechanism. The main thermal degradation pathway of the composites was the β-hydrogen scission of the polymeric backbone. In conclusion, this study provides information about the thermal behavior of PESu/hemp fiber composites useful for their application as alternative “wood plastic composites (WPCs)”.

Polyplexes of DNA and Poly(l-lysine) Stabilized by Au Nanoparticles for Targeted Photothermal Therapy

DNA polyplexes are classic nanomaterials used in the field of gene delivery because of their controllable biodegradability and biocompatibility. However, nanofabrication of DNA polyplexes as an organic building block has rarely been investigated, probably because of their low chemical and physical stability under various reaction conditions. In this study, we present the synthesis of highly stable DNA-poly-l-lysine (PLL) polyplexes and their use as cores to synthesize uniform gold nanoshells for photothermal therapy. To stabilize the DNA-PLL polyplexes, we introduced gold nanoparticles (AuNPs) to the polyplex surface (poly@AuNPs) through electrostatic and coordinate interactions of AuNPs with PLL and DNA, which significantly enhances the chemical and physical stability of the polyplexes, while maintaining their enzymatic biodegradability. Importantly, poly@AuNPs are suitable organic templates for the synthesis of polyplex core@gold nanoshells (poly@AuNSs) that exhibit excellent photothermal properties, high photothermal stability, and outstanding targeting ability toward cancer cells. The photothermal application of FA-modified poly@AuNSs for the elimination of tumors was practically demonstrated using nude mice. This study is the first demonstration of poly@AuNPs as chemically and physically stable yet biodegradable cores for nanoshell formation and, consequently, biomedical therapy, which sheds light on their potential applications in bioimaging, contrast agents, and organic templates for the synthesis of other functional nanostructures.

In Vitro Biodegradation, Drug Absorption, and Physical Properties of Gelatin–Fucoidan Microspheres Made of Subcritical-Water-Modified Fish Gelatin

This study aimed to prepare gelatin-fucoidan microspheres with enhanced doxorubicin binding efficiency and controllable biodegradation using fish gelatin combined with low molecular weight (LMW) gelatin and fucoidan at fixed ratios. The MW of gelatin was modified by subcritical water (SW), which is known as a safe solvent, at 120 °C, 140 °C, and 160 °C. In addition, gelatin-fucoidan microspheres were prepared using a solvent exchange technique. Our findings revealed that particle size decreased, the surface was rougher, the swelling ratio increased, and particle shape was irregular in microspheres composed of SW-modified gelatin. Doxorubicin binding efficiency was improved by fucoidan and SW-modified gelatin at 120 °C but not at 140 °C and 160 °C. Interestingly, an increase in in vitro enzymatic degradation was observed in the microspheres consisting of SW-modified fish gelatin, although the cross-linking degree between them was not significantly different. This is because LMW gelatin could form more cross-linked bonds, which might be weaker than the intramolecular bonds of gelatin molecules. Gelatin-fucoidan microspheres consisting of SW-modified fish gelatin with controlled biodegradation rates could be a candidate for a short-term transient embolization agent. In addition, SW would be a promising method to modify the MW of gelatin for medical applications.

Emerging Trends in Biodegradable Microcarriers for Therapeutic Applications.

Microcarriers (MCs) are adaptable therapeutic instruments that may be adjusted to specific therapeutic uses, making them an appealing alternative for regenerative medicine and drug delivery. MCs can be employed to expand therapeutic cells. MCs can be used as scaffolds for tissue engineering, as well as providing a 3D milieu that replicates the original extracellular matrix, facilitating cell proliferation and differentiation. Drugs, peptides, and other therapeutic compounds can be carried by MCs. The surface of the MCs can be altered, to improve medication loading and release, and to target specific tissues or cells. Allogeneic cell therapies in clinical trials require enormous volumes of stem cells, to assure adequate coverage for several recruitment locations, eliminate batch to batch variability, and reduce production costs. Commercially available microcarriers necessitate additional harvesting steps to extract cells and dissociation reagents, which reduces cell yield and quality. To circumvent such production challenges, biodegradable microcarriers have been developed. In this review, we have compiled key information relating to biodegradable MC platforms, for generating clinical-grade cells, that permit cell delivery at the target site without compromising quality or cell yields. Biodegradable MCs could also be employed as injectable scaffolds for defect filling, supplying biochemical signals for tissue repair and regeneration. Bioinks, coupled with biodegradable microcarriers with controlled rheological properties, might improve bioactive profiles, while also providing mechanical stability to 3D bioprinted tissue structures. Biodegradable materials used for microcarriers have the ability to solve in vitro disease modeling, and are advantageous to the biopharmaceutical drug industries, because they widen the spectrum of controllable biodegradation and may be employed in a variety of applications.

Photosynthetic microporous bioactive glass ceramic beads for treating avascular osteonecrosis

Bioactive glass (BG) ceramics have attracted considerable attention as ideal bone grafts for treating avascular osteonecrosis owing to similarities in biological function with that of native bone. Metal ion-doped BGs exhibit outstanding biocompatibility, controllable biodegradability, excellent osteoinductivity, and angiogenic ability. Moreover, effective oxygen generation can support the healing of osteonecrotic defects. In this study, we developed simple sol–gel, gel-casting, and surface modification methods to fabricate photosynthetic microporous BG ceramic beads with improved therapeutic efficacy for avascular osteonecrosis by combining the oxygen generation ability, osteoconductivity, osteoinductivity, and angiogenic ability. The BG ceramic beads exhibited interconnected microporous structures with uniform micropores and unequiaxed grains, and this microstructure was not affected by Sr- and Cu-co-doping. Conversely, Sr- and Cu-co-doping, epigallocatechin gallate immobilization, and thylakoid coating affected the in vitro biological activity of the BG ceramic beads. Biological activity assays revealed that the thylakoid-coated photosynthetic microporous BG (BG12ET) ceramic beads promoted osteoblastic cell proliferation and endothelial cell tube formation more effectively than other ceramic beads. Therefore, BG12ET ceramic beads incorporated with osteoinductive and angiogenic factors can potentially provide a new generation of bone grafts for synergistic osteonecrosis therapy.

Composite PLGA–Nanobioceramic Coating on Moxifloxacin-Loaded Akermanite 3D Porous Scaffolds for Bone Tissue Regeneration

Silica-based ceramics doped with calcium and magnesium have been proposed as suitable materials for scaffold fabrication. Akermanite (Ca2MgSi2O7) has attracted interest for bone regeneration due to its controllable biodegradation rate, improved mechanical properties, and high apatite-forming ability. Despite the profound advantages, ceramic scaffolds provide weak fracture resistance. The use of synthetic biopolymers such as poly(lactic-co-glycolic acid) (PLGA) as coating materials improves the mechanical performance of ceramic scaffolds and tailors their degradation rate. Moxifloxacin (MOX) is an antibiotic with antimicrobial activity against numerous aerobic and anaerobic bacteria. In this study, silica-based nanoparticles (NPs) enriched with calcium and magnesium, as well as copper and strontium ions that induce angiogenesis and osteogenesis, respectively, were incorporated into the PLGA coating. The aim was to produce composite akermanite/PLGA/NPs/MOX-loaded scaffolds through the foam replica technique combined with the sol-gel method to improve the overall effectiveness towards bone regeneration. The structural and physicochemical characterizations were evaluated. Their mechanical properties, apatite forming ability, degradation, pharmacokinetics, and hemocompatibility were also investigated. The addition of NPs improved the compressive strength, hemocompatibility, and in vitro degradation of the composite scaffolds, resulting in them keeping a 3D porous structure and a more prolonged release profile of MOX that makes them promising for bone regeneration applications.

A Comprehensive Review on Silk Fibroin as a Persuasive Biomaterial for Bone Tissue Engineering.

Bone tissue engineering (BTE) utilizes a special mix of scaffolds, cells, and bioactive factors to regulate the microenvironment of bone regeneration and form a three-dimensional bone simulation structure to regenerate bone tissue. Silk fibroin (SF) is perhaps the most encouraging material for BTE given its tunable mechanical properties, controllable biodegradability, and excellent biocompatibility. Numerous studies have confirmed the significance of SF for stimulating bone formation. In this review, we start by introducing the structure and characteristics of SF. After that, the immunological mechanism of SF for osteogenesis is summarized, and various forms of SF biomaterials and the latest development prospects of SF in BTE are emphatically introduced. Biomaterials based on SF have great potential in bone tissue engineering, and this review will serve as a resource for future design and research.

Biodegradable PLA-ZnO nanocomposite biomaterials with antibacterial properties, tissue engineering viability, and enhanced biocompatibility

Polylactic acid (PLA) is a well-known biomaterial on account of its biocompatibility and biodegradability. Zinc oxide (ZnO) nanofillers may endow PLA with advantageous antibacterial and tissue regenerative properties, but may also compromise the biocompatibility of PLA. Several strategies have been developed to improve the biomedical practicality of such composites. The importance of surface properties on amplifying the therapeutic properties and safety of a material enables two potential strategies: (i) surface modification of ZnO nanoparticles, and (ii) surface engineering of the PLA/ZnO composites. Moreover, the controllable biodegradation of PLA allows a third possible strategy: (iii) biodegradation-controlled release of ZnO. The first part of this review introduces the controllable degradation of PLA and the mechanisms of therapeutic properties and cytotoxicity of ZnO. Following this, the paper highlights current research trends regarding the biomedical application of PLA-based ZnO nanocomposites. The final section of this review discusses the potential use of ZnO in tuning the degradation rate of PLA, and the possibility of manipulating the surface properties of ZnO nanoparticles and PLA/ZnO composites in order to optimize the therapeutic properties and safe usage of PLA/ZnO composites in the biomedical field.

Recent advances of medical polyhydroxyalkanoates in musculoskeletal system.

Infection and rejection in musculoskeletal trauma often pose challenges for natural healing, prompting the exploration of biomimetic organ and tissue transplantation as a common alternative solution. Polyhydroxyalkanoates (PHAs) are a large family of biopolyesters synthesised in microorganism, demonstrating excellent biocompatibility and controllable biodegradability for tissue remodelling and drug delivery. With different monomer-combination and polymer-types, multi-mechanical properties of PHAs making them have great application prospects in medical devices with stretching, compression, twist in long time, especially in musculoskeletal tissue engineering. This review systematically summarises the applications of PHAs in multiple tissues repair and drug release, encompassing areas such as bone, cartilage, joint, skin, tendons, ligament, cardiovascular tissue, and nervous tissue. It also discusses challenges encountered in their application, including high production costs, potential cytotoxicity, and uncontrollable particle size distribution. In conclusion, PHAs offer a compelling avenue for musculoskeletal system applications, striking a balance between biocompatibility and mechanical performance. However, addressing challenges in their production and application requires further research to unleash their full potential in tackling the complexities of musculoskeletal regeneration.

Silk fibroin scaffolds: A promising candidate for bone regeneration.

It remains a big challenge in clinical practice to repair large-sized bone defects and many factors limit the application of autografts and allografts, The application of exogenous scaffolds is an alternate strategy for bone regeneration, among which the silk fibroin (SF) scaffold is a promising candidate. Due to the advantages of excellent biocompatibility, satisfying mechanical property, controllable biodegradability and structural adjustability, SF scaffolds exhibit great potential in bone regeneration with the help of well-designed structures, bioactive components and functional surface modification. This review will summarize the cell and tissue interaction with SF scaffolds, techniques to fabricate SF-based scaffolds and modifications of SF scaffolds to enhance osteogenesis, which will provide a deep and comprehensive insight into SF scaffolds and inspire the design and fabrication of novel SF scaffolds for superior osteogenic performance. However, there still needs more comprehensive efforts to promote better clinical translation of SF scaffolds, including more experiments in big animal models and clinical trials. Furthermore, deeper investigations are also in demand to reveal the degradation and clearing mechanisms of SF scaffolds and evaluate the influence of degradation products.

Fabrication and Characterization of Novel Silk Fiber-Optic SERS Sensor with Uniform Assembly of Gold Nanoparticles.

Biocompatible optical fibers and waveguides are gaining attention as promising platforms for implantable biophotonic devices. Recently, the distinct properties of silk fibroin were extensively explored because of its unique advantages, including flexibility, process compatibility, long-term biosafety, and controllable biodegradability for in vitro and in vivo biomedical applications. In this study, we developed a novel silk fiber for a sensitive optical sensor based on surface-enhanced Raman spectroscopy (SERS). In contrast to conventional plasmonic nanostructures, which employ expensive and time-consuming fabrication processes, gold nanoparticles were uniformly patterned on the top surface of the fiber employing a simple and cost-effective convective self-assembly technique. The fabricated silk fiber-optic SERS probe presented a good performance in terms of detection limit, sensitivity, and linearity. In particular, the uniform pattern of gold nanoparticles contributed to a highly linear sensing feature compared to the commercial multi-mode fiber sample with an irregular and aggregated distribution of gold nanoparticles. Through further optimization, silk-based fiber-optic probes can function as useful tools for highly sensitive, cost-effective, and easily tailored biophotonic platforms, thereby offering new capabilities for future implantable SERS devices.

Selected Simple Natural Antimicrobial Terpenoids as Additives to Control Biodegradation of Polyhydroxy Butyrate.

In this experimental research, different types of essential oils (EOs) were blended with polyhydroxybutyrate (PHB) to study the influence of these additives on PHB degradation. The blends were developed by incorporating three terpenoids at two concentrations (1 and 3%). The mineralization rate obtained from CO2 released from each sample was the factor that defined biodegradation. Furthermore, scanning electron microscope (SEM), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA) were used in this research. The biodegradation percentages of PHB blended with 3% of eucalyptol, limonene, and thymol after 226 days were reached 66.4%, 73.3%, and 76.9%, respectively, while the rate for pure PHB was 100% after 198 days, and SEM images proved these results. Mechanical analysis of the samples showed that eucalyptol had the highest resistance level, even before the burial test. The other additives showed excellent mechanical properties although they had less mechanical strength than pure PHB after extrusion. The samples' mechanical properties improved due to their crystallinity and decreased glass transition temperature (Tg). DSC results showed that blending terpenoids caused a reduction in Tg, which is evident in the DMA results, and a negligible reduction in melting point (Tm).