Multifunctional Biomaterials Research Articles

Valorization of nano-based lignocellulosic derivatives to procure commercially significant value-added products for biomedical applications

Biowaste, produced from nature, is preferred to be a good source of carbon and ligninolytic machinery for many microorganisms. They are complex biopolymers composed of lignin, cellulose, and hemicellulose traces. This biomass can be depolymerized to its nano-dimensions to gain exceptional properties useful in the field of cosmetics, pharmaceuticals, high-strength materials, etc. Nano-sized biomass derivatives overcome the inherent drawbacks of the parent material and offer promises as a potential material for a wide range of applications with their unique traits such as low-toxicity, biocompatibility, biodegradability and environmentally friendly nature with versatility. This review focuses on the production of value–added products feasible from nanocellulose, nano lignin, and xylan nanoparticles which is quite a novel study of its kind. Dawn of nanotechnology has converted bio waste by–products (hemicellulose and lignin) into useful precursors for many commercial products. Nano-cellulose has been employed in the fields of electronics, cosmetics, drug delivery, scaffolds, fillers, packaging, and engineering structures. Xylan nanoparticles and nano lignin have numerous applications as stabilizers, additives, textiles, adhesives, emulsifiers, and prodrugs for many polyphenols with an encapsulation efficiency of 50%. This study will support the potential development of composites for emerging applications in all aspects of interest and open up novel paths for multifunctional biomaterials in nano-dimensions for cosmetic, drug carrier, and clinical applications.

In situ gelation strategy based on ferrocene-hyaluronic acid organic copolymer biomaterial for exudate management and multi-modal wound healing

Exudate management remains a major concern in slow or non-healing wound management. Therefore, there is a need to devise a massive exudate-absorbing, exudate-locking, and stable extracellular matrix structure-maintaining functional wound dressing. Inspired by metal-organic frameworks, we chemically introduced sandwich ferrocene (Fc) into hyaluronic acid (HA) to fabricate an innovative metal Fc-HA organic copolymer (FHoC) as the skeleton material for in situ gelation, which was then gently compressed into a pre-hydrogel patch (FHoCP). Fc promoted the rearrangement of polymer chains to form additional microcrystalline and hydrophobic regions, which improved hydrogel transition and the exudate-locking ability. Thus, the simple composition FHoCP(5) absorbed 150 times its weight of water and maintained a firm three-dimensional network, which contributed to reducing inflammation and acted as a physical barrier against hemostasis and anti-bacterial invasion. Meanwhile, multi-modal processes, including fibroblast migration, angiogenesis, and antibacterial effects, were integrated into the gelled FHoCP(5) guided by Fe to promote wound healing. This study suggested that FHoC biomaterial could accelerate the closure of chronic wounds. We believe that this unique FHoCP(5)-based in situ gelation strategy could provide a solid drug-loaded scaffold for cell or adjunctive drug therapies, which holds great potential for the development of multifunctional biomaterials. Statement of significanceHydrogels that absorb excessive exudates while maintaining stable ECM-like network as well as exert multimodal wound healing activities are ideal dressings for accelerating chronic wound contraction. Herein, we reported an innovative metal ferrocene-hyaluronic acid organic copolymer patch (FHoCP) and FHoCP-mediated in situ gelation strategy. Ferrocene (Fc) induced in situ gelation by promoting polymer chain rearrangement, acting as a physical barrier for hemostasis and anti-bacterial invasion, and absorbing massive exudates, resulting in reducing delayed inflammation. As the structural core, rigid Fc enhanced the stability of the hydrogel backbone, and hydrophobic Fc improved fibroblast migration. In addition, Fe2+ chemically inhibited bacteria and increased angiogenesis. These results indicated the potential of FHoCP-based hydrogel for application in clinical skin reconstruction.

Structural Requirement of hA5G18 Peptide (DDFVFYVGGYPS) from Laminin α5 Chain for Amyloid-like Fibril Formation and Cell Adhesion.

The hA5G18 peptide (DDFVFYVGGYPS) identified from the human laminin α5 chain G domain promotes cell attachment and spreading when directly coated on a plastic plate, but does not show activity when it is conjugated on a chitosan matrix. Here, we focused on the structural requirement of hA5G18 for activity. hA5G18 was stained with Congo red and formed amyloid-like fibrils. A deletion analysis of hA5G18 revealed that FVFYV was a minimum active sequence for the formation of amyloid-like fibrils, but FVFYV did not promote cell attachment. Next, we designed functional fibrils using FVFYV as a template for amyloid-like fibrils. When we conjugated an integrin binding sequence Arg-Gly-Asp (RGD) to the FVFYV peptide with Gly-Gly (GG) as a spacer, FVFYVGGRGD promoted cell attachment in a plate coat assay, but a negative control sequence RGE conjugated peptide, FVFYVGGRGE, also showed activity. However, when the peptides were conjugated to Sepharose beads, the FVFYVGGRGD beads showed cell attachment activity, but the FVFYVGGRGE beads did not. These results suggest that RGD and RGE similarly contribute to cell attachment activity in amyloid-like fibrils, but only RGD contributes the activity on the Sepharose beads. Further, we conjugated a basic amino acid (Arg, Lys, and His) to the FVFYV peptide. Arg or Lys-conjugated FVFYV peptides, FVFYVGGR and FVFYVGGK, showed cell attachment activity when they were coated on a plate, but a His-conjugated FVFYV peptide FVFYVGGH did not show activity. None of the basic amino acid-conjugated peptides showed cell attachment in a Sepharose bead assay. The cell attachment and spreading on FVFYVGGR and FVFYVGGK were inhibited by an anti-integrin β1 antibody. These results suggest that the Arg and Lys residues play critical roles in the interaction with integrins in amyloid-like fibrils. FVFYV is useful to use as a template for amyloid-like fibrils and to develop multi-functional biomaterials.

Reproducible and controlled peptide functionalization of polymeric nanoparticles

Polymeric nanoparticles containing multiple amines and carboxylates have been frequently used in drug delivery research. Reproducible and controlled conjugation among these multifunctional biomaterials is necessary to achieve efficient drug delivery platforms. However, multiple functional groups increase the risk of unintended intramolecular/intermolecular reactions during conjugation. Herein, conjugation approaches and possible undesired reactions between multi-amine functionalized peptides, multi-carboxylate functionalized polymers, and anhydride-containing polymers [Poly(styrene-alt-maleic anhydride)-b-poly(styrene)] were investigated under different conjugation strategies (carbodiimide chemistry, anhydride ring-opening via nucleophilic addition elimination). Muti-amine peptides led to extensive crosslinking between polymers regardless of the conjugation chemistry. Results also indicate that conventional peptide quantification methods (i.e., o-phthalaldehyde assay, bicinchoninic acid assay) are unreliable. Gel permeation chromatography (GPC) provided more accurate qualitative and quantitative evidence for intermolecular crosslinking. Crosslinking densities were correlated with higher feed ratios of multifunctional peptides and carbodiimide coupling reagents. Selectively protected peptides (Lys-Alloc) exhibited no crosslinking and yielded peptide-polymer conjugates with controlled dispersity and molecular weight. Furthermore, anhydride ring-opening (ARO) nucleophilic addition elimination was successfully introduced as a facile yet robust peptide conjugation approach for cyclic anhydride-containing polymers.

Contact-Active Layer-by-Layer Grafted TPU/PDMS Blends as an Antiencrustation and Antibacterial Platform for Next-Generation Urological Biomaterials: Validation in Artificial and Human Urine.

Urinary tract infections and urinary encrustation impede the long-term clinical performance of urological implants and medical devices. Together, biofilm formation and encrustation constitute serious complications, driving the development of next-generation urological biomaterials. The currently available bioengineered solutions have limited success during long-term usage in the urinary environment. In addressing this unmet clinical challenge, contact-active, antiencrustation surface grafting were conceived onto a dynamically cross-linked polydimethylsiloxane (PDMS) modified thermoplastic polyurethane (TPU) blend using the layer-by-layer (LbL) assembly route. To the best of the authors' knowledge, the present study is the first to investigate the LbL grafting in developing an antiencrustation platform. These multilayered assemblies strategically employed covalent cross-linking and electrostatic interaction-assisted progressive depositions of branched polyethyleneimine and poly(2-ethyl-2-oxazoline). While polyethyleneimine conferred the contact-killing bactericidal activity, the much-coveted antiencrustation properties were rendered by incorporating a partially hydrolyzed derivative of poly(2-ethyl-2-oxazoline). The performance of the resultant surface-modified TPU/PDMS blends was benchmarked against the conventional urological alloplasts, in a customized lab-scale bioreactor-based dynamic encrustation study and in human urine. After 6 weeks of exposure to an artificial urine medium, simulating urease-positive bacterial infection, the surface-modified blends exhibited a remarkable ability to suppress Ca and Mg encrustation. In addition, these blends also displayed superior grafting stability and antibacterial efficacy against common uropathogens. As high as 4-fold log reduction in the planktonic growth of Gram-negative P. mirabilis and Gram-positive MRSA was recorded with the LbL platform vis-à-vis medical-grade TPU. In conjunction, the in vitro cellular assessment with human keratinocytes (HaCaT) and human embryonic kidney cells (HEK) established the uncompromised cytocompatibility of the multilayered grafted blends. Finally, the physiologically relevant functionality of the LbL grafting has been validated using clinical samples of human urine collected from 129 patients with a broad spectrum of disease conditions. The phase-I pre-clinical study, entailing 6 week-long incubation in human urine, demonstrated significantly improved encrustation resistance of the blends. The collective findings of the present work clearly establish the success of LbL strategies in the development of stable, multifunctional new-generation urological biomaterials.

Injectable adhesive self-healing biocompatible hydrogel for haemostasis, wound healing, and postoperative tissue adhesion prevention in nephron-sparing surgery

Nephron-sparing surgery is a well-established treatment in patients with T1a renal cell carcinoma; however, the complex suturing process prolongs warm ischaemia time, affects the preservation of normal renal parenchymal function, and causes avoidable postoperative tissue adhesion complications, including chronic abdominal pain, intestinal obstruction, and female infertility. Hence, the design of multifunctional biomaterials with haemostasis, postoperative wound management, and postoperative tissue adhesion prevention properties for nephron-sparing surgeries is urgently needed. In this study, a series of injectable adhesive multifunctional biocompatible hydrogels were designed based on the free-radical polymerisation of monomers acryloyl-6-aminocaproic acid (AA) and N-acryloyl 2-glycine (NAG), and the ionic coordination between Ca2+ and the abundant carboxyl groups in AA and NAG. AA/NAG/Ca (AA, NAG, and Ca refer to acryloyl-6-aminocaproic acid, N-acryloyl 2-glycine and calcium chloride, respectively) hydrogel exhibited good mechanical properties, swelling and adhesion properties, flexibility, in vitro blood-clotting ability, and cytocompatibility. In vivo experiments on liver injury models and rat/rabbit nephron-sparing surgery models elucidated that the AA/NAG/Ca hydrogel had haemostasis performance and wound healing properties that led to short bleeding time, reduced bleeding volume, and well-organised nephron structures. An abdomen-caecum adhesion model indicated that the AA/NAG/Ca hydrogel showed excellent anti-adhesion properties. In summary, this multifunctional hydrogel exhibited potential for improving haemostasis and wound management in nephron-sparing surgeries, showing potential for clinical application. Statement of significanceExtended warm ischemia time during nephron sparing surgery negatively affected postoperative renal function due to the need for hemostasis at the wound with abundant blood supply, and postoperative wound healing and additional adhesions caused by the surgical procedure deserve attention. Based on the efficient and stable adhesion properties of hydrogels and the ability to promote wound healing. Herein, a series of adhesive self-healing biocompatible hydrogels were prepared based on free-radical polymerization of acryloyl-6-aminocaproic acid (AA) and N-acryloyl 2-glycine (NAG) and the ionic coordination between Ca2+ with the abundant carboxyl groups in AA and NAG. AA/NAG/Ca hydrogel showed hemostasis property in nephron sparing surgery model, promote kidney wound healing, and could perform anti-postoperative adhesion efficacy in an abdomen-caecum adhesion model.

Electrospun Collagen Scaffold Bio-Functionalized with Recombinant ICOS-Fc: An Advanced Approach to Promote Bone Remodelling.

The treatment of osteoporotic fractures is a severe clinical issue, especially in cases where low support is provided, e.g., pelvis. New treatments aim to stimulate bone formation in compromised scenarios by using multifunctional biomaterials combined with biofabrication techniques to produce 3D structures (scaffolds) that can support bone formation. Bone’s extracellular matrix (ECM) is mainly composed of type I collagen, making this material highly desirable in bone tissue engineering applications, and its bioactivity can be improved by incorporating specific biomolecules. In this work, type I collagen membranes were produced by electrospinning showing a fibre diameter below 200 nm. An optimized one-step strategy allowed to simultaneously crosslink the electrospun membranes and bind ICOS-Fc, a biomolecule able to reversibly inhibit osteoclast activity. The post-treatment did not alter the ECM-like nanostructure of the meshes and the physicochemical properties of collagen. UV-Vis and TGA analyses confirmed both crosslinking and grafting of ICOS-Fc onto the collagen fibres. The preservation of the biological activity of grafted ICOS-Fc was evidenced by the ability to affect the migratory activity of ICOSL-positive cells. The combination of ICOS-Fc with electrospun collagen represents a promising strategy to design multifunctional devices able to boost bone regeneration in osteoporotic fractures.

3D Printing of Cellulase-Laden Cellulose Nanofiber/Chitosan Hydrogel Composites: Towards Tissue Engineering Functional Biomaterials with Enzyme-Mediated Biodegradation.

The 3D printing of a multifunctional hydrogel biomaterial with bioactivity for tissue engineering, good mechanical properties and a biodegradability mediated by free and encapsulated cellulase was proposed. Bioinks of cellulase-laden and cellulose nanofiber filled chitosan viscous suspensions were used to 3D print enzymatic biodegradable and biocompatible cellulose nanofiber (CNF) reinforced chitosan (CHI) hydrogels. The study of the kinetics of CNF enzymatic degradation was studied in situ in fibroblast cell culture. To preserve enzyme stability as well as to guarantee its sustained release, the cellulase was preliminarily encapsulated in chitosan–caseinate nanoparticles, which were further incorporated in the CNF/CHI viscous suspension before the 3D printing of the ink. The incorporation of the enzyme within the CHI/CNF hydrogel contributed to control the decrease of the CNF mechanical reinforcement in the long term while keeping the cell growth-promoting property of chitosan. The hydrolysis kinetics of cellulose in the 3D printed scaffolds showed a slow but sustained degradation of the CNFs with enzyme, with approximately 65% and 55% relative activities still obtained after 14 days of incubation for the encapsulated and free enzyme, respectively. The 3D printed composite hydrogels showed excellent cytocompatibility supporting fibroblast cell attachment, proliferation and growth. Ultimately, the concomitant cell growth and biodegradation of CNFs within the 3D printed CHI/CNF scaffolds highlights the remarkable potential of CHI/CNF composites in the design of tissue models for the development of 3D constructs with tailored in vitro/in vivo degradability for biomedical applications.

A dual-responsive polydopamine-modified hydroxybutyl chitosan hydrogel for sequential regulation of bone regeneration

Delayed inflammatory reaction and poor osteogenesis are the two main causes of failure for bone-defect healing. Accordingly, in the present study, a dual-responsive hydrogel composite was successfully fabricated in which near-infrared (NIR)-light-responsive polydopamine-coated magnesium‐calcium carbonate microspheres are incorporated into a thermo-responsive hydroxybutyl chitosan hydrogel to provide sequential delivery of the anti-inflammatory drug aspirin and osteogenic bone morphogenetic protein 2 (BMP-2). By initially releasing aspirin rapidly, the hydrogel composite efficiently ameliorates early-stage inflammatory reaction and promotes transition to the regenerative phase. Then, the hydrogel composite allows NIR-light-responsive release of BMP-2, which maximizes its osteoinductive effects. Using an SD rat calvaria-defect model, the sequential and controllable release achieved by the hydrogel is demonstrated to promote new-bone formation. Thus, the current study provides an efficient alternative strategy for developing multifunctional therapeutic biomaterials for bone tissue engineering.

Nanomaterials: A powerful tool for tumor immunotherapy.

Cancer represents the leading global driver of death and is recognized as a critical obstacle to increasing life expectancy. In recent years, with the development of precision medicine, significant progress has been made in cancer treatment. Among them, various therapies developed with the help of the immune system have succeeded in clinical treatment, recognizing and killing cancer cells by stimulating or enhancing the body’s intrinsic immune system. However, low response rates and serious adverse effects, among others, have limited the use of immunotherapy. It also poses problems such as drug resistance and hyper-progression. Fortunately, thanks to the rapid development of nanotechnology, engineered multifunctional nanomaterials and biomaterials have brought breakthroughs in cancer immunotherapy. Unlike conventional cancer immunotherapy, nanomaterials can be rationally designed to trigger specific tumor-killing effects. Simultaneously, improved infiltration of immune cells into metastatic lesions enhances the efficiency of antigen submission and induces a sustained immune reaction. Such a strategy directly reverses the immunological condition of the primary tumor, arrests metastasis and inhibits tumor recurrence through postoperative immunotherapy. This paper discusses several types of nanoscale biomaterials for cancer immunotherapy, and they activate the immune system through material-specific advantages to provide novel therapeutic strategies. In summary, this article will review the latest advances in tumor immunotherapy based on self-assembled, mesoporous, cell membrane modified, metallic, and hydrogel nanomaterials to explore diverse tumor therapies.

Covalent Organic Framework (COF): A Drug and Carrier to Attenuate Retinal Ganglion Cells Death in an Acute Glaucoma Mouse Model

Purpose: We aim to investigate the use of covalent organic framework (COF) nanoparticles in the local treatment of glaucoma, both as a means of protecting retinal ganglion cells (RGCs), and as a carrier for delayed release of the medication rapamycin following a single intravitreal injection. Methods: a water-dispersible COF, and a COF-based nanoplatform for rapamycin release (COF-Rapa) was constructed. C57BL/6J mice were randomly divided into four groups: intravitreal injection of 1.5 µL normal saline (NS), COF (0.67 ng/µL), rapamycin (300 µM) or COF-Rapa (0.67 ng/µL-300 µM), respectively. The ischemia–reperfusion (I/R) model was established to mimic high intraocular pressure (IOP)-induced retinal injury in glaucoma. Labeling of RGCs by Fluoro-Gold and retinal electroretinogram were used to evaluate retinal function. Immunohistochemistry and Western blotting analyses of retinas were performed. Results: COF nanoparticles were delivered in vitro and in vivo. Six weeks after the COF injection, the number of RGCs was unaffected. In addition, the number of RBPMS-positive RGCs, GFAP-positive astrocytes and Iba1-positive microglia did not differ from the normal control. COF could effectively reduce RGCs death, improve phototransduction function and alleviate the overactivation of microglia compared to NS control after retinal I/R injury. Within six weeks, the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in the retinas could be inhibited by a single intravitreal injection of COF-Rapa. Compared with single COF administration, COF-Rapa significantly reduced the inflammatory reaction after retinal I/R injury. Conclusions: COF may act as both an RGC protection agent and a carrier for prolonged rapamycin release. This research may lead to the development of novel RGC protection agents and drug delivery techniques, as well as the creation of multifunctional COF-based biomaterials for glaucoma retinopathy.

Enzyme-driven oxygen-fuelled pathway selectivity of tyrosine-containing peptide oxidation evolution

The pathway selectivity of chemical evolution controlled by enzymes, with proteins and peptides as substrates, is of critical significance to determine biological processes and functions. In nature, organisms utilize tyrosinase to catalyse oxidation reactions of tyrosine to produce multifunctional compounds in different pathways. However, it remains a great challenge to manipulate the pathway selection of tyrosinase-guided chemical evolution for achieving biomaterials with on-demand functions. We herein report that controlling oxygen concentration is effective in regulating the evolution of tyrosinase-catalysed oxygenation pathways of tyrosine-containing peptides and even proteins. The melanin formation pathway predominates under oxygen-enriched conditions, while fluorescent compounds are preferentially generated under hypoxic conditions. The chemical evolution of tyrosine-containing peptides, regardless of their neighbouring amino acid types and sequences, tends to be governed by these two competitive pathways. These competitive pathways are manipulated by conformational transformation of tyrosinase active centre that is determined by oxygen concentration. Moreover, the oxygen-controlled chemical evolution of tyrosine-containing biomolecules can be broadly realized by tyrosinase to obtain melanin-based photothermal materials or multicolour fluorescent materials. This work reveals the plausible role of oxygen in the pathway selectivity of enzyme-controlled chemical evolution of tyrosine-containing peptides and verifies the possibility of fluorescent detection in living cultured melanoma cells, which provides a versatile strategy for precise design and engineering of tyrosine-involved multifunctional biomaterials.

Optimization of Multilayer Films Composed of Chitosan and Low-Methoxy Amidated Pectin as Multifunctional Biomaterials for Drug Delivery.

Polyelectrolyte multilayers (PEMs) based on polyelectrolyte complex (PEC) structures are recognized as interesting materials for manufacturing functionalized coatings or drug delivery platforms. Difficulties in homogeneous PEC system development generated the idea of chitosan (CS)/low-methoxy amidated pectin (LM PC) multilayer film optimization with regard to the selected variables: the polymer ratio, PC type, and order of polymer mixing. Films were formulated by solvent casting method and then tested to characterize CS/LM PC PECs, using thermal analysis, Fourier transform infrared spectroscopy (FTIR), turbidity, and zeta potential measurements. The internal structure of the films was visualized by using scanning electron microscopy. Analysis of the mechanical and swelling properties enabled us to select the most promising formulations with high uniformity and mechanical strength. Films with confirmed multilayer architecture were indicated as a promising material for the multifunctional systems development for buccal drug delivery. They were also characterized by improved thermal stability as compared to the single polymers and their physical mixtures, most probably as a result of the CS–LM PC interactions. This also might indicate the potential protective effect on the active substances being incorporated in the PEC-based films.

Self-Assembly of a Multifunction DNA Tetrahedron for Effective Delivery of Aptamer PL1 and Pcsk9 siRNA Potentiate Immune Checkpoint Therapy for Colorectal Cancer.

Compared with the traditional single therapy, nanomedicine has promoted a multimodal combination treatment for various carcinomas, especially the development of corresponding intelligent multifunctional biomaterials based on advanced DNA nanotechnology has great potential in cancer combination therapy. Herein, we describe a strategy to “backpack” aptamer PL1, which specifically binds to PD-L1 and Pcsk9 siRNA on well-defined DNA tetrahedral nanoparticles (TDNs) via DNA hybridization, which collectively contributes to the effective therapy for colorectal cancer (CRC). In addition, we designed a targeted TDN upon folic acid (FA) recognition, limiting its release to the sites of tumors where folic acid receptor (FAR) is encountered. Our results demonstrated that the TDN-FA/PL1/Pcsk9-siRNA could free immune cells to target CRC cells and attenuate 83.48% tumor growth in mouse models of CT26 CRC. Mechanically, the cancer-targeting FA guided TDN-FA/PL1/Pcsk9-siRNA into tumor cells, thereby ensuring that the aptamer PL1 could choke the mutual effects between PD-1 and PD-L1, followed by a 1.69-fold increase in T cell number and a 1.9-fold suppression of T cell activity by the PD-1/PD-L1 pathway, while Pcsk9 siRNA decreased Pcsk9 expression averagely to the extent of 65.13% and then facilitated intratumoral infiltration of cytotoxic T cells robustly with IFN-γ and Granzyme B expression. Our results reveal that the multifunctional TND-FA/PL1/Pcsk9-siRNA is effective and safe for CRC therapy, thereby expanding the application of DNA nanotechnology for innovative therapies of various cancers.

Regenerative Role of T Cells in Nerve Repair and Functional Recovery.

The immune system is essential in the process of nerve repair after injury. Successful modulation of the immune response is regarded as an effective approach to improving treatment outcomes. T cells play an important role in the immune response of the nervous system, and their beneficial roles in promoting regeneration have been increasingly recognized. However, the diversity of T-cell subsets also delivers both neuroprotective and neurodegenerative functions. Therefore, this review mainly discusses the beneficial impact of T-cell subsets in the repair of both peripheral nervous system and central nervous system injuries and introduces studies on various therapies based on T-cell regulation. Further discoveries in T-cell mechanisms and multifunctional biomaterials will provide novel strategies for nerve regeneration.

Quaternary bioactive glass-derived powders presenting submicrometric particles and antimicrobial activity

The biomedical engineering advances in the last years have been rising demand for multifunctional biomaterials. Bioactive glass (BG) submicron particles are potential candidates for the formulation of composites with improved dispersion and homogeneity between the constituents. This work presents the preparation of SiO2–Na2O–CaO–P2O5 glass-derived powders composed of particles with homogenous shapes and sizes between 300 and 500 nm. Two types of synthesis were employed for the preparation of the BG powders, the melt-quenching method, and a citric acid-assisted sol-gel route at a low citric acid concentration (0.005 mol L−1). The morphology of the particles was achieved by a low-energy process using a ball mill. These powders were characterized for their structure and surface area and evaluated for in vitro mineralization and antibacterial behavior. X-ray diffraction (XRD) analysis revealed different crystalline silicate phases in the sol-gel-derived powder and confirmed the amorphous structure of the melt-quenching-derived one. The surface of the particles was covered by hydroxycarbonate-apatite (HCA) after five days in simulated body fluid (SBF). The antibacterial activity against Staphylococcus aureus was higher for the sol-gel-derived powder, showing inhibition >99% of the bacteria growth in 24 h for all concentrations studied. These BG-based powders present a set of characteristics useful for the formulation of multifunctional composites for orthopedic applications.

Development and characterization of natural rubber latex wound dressings enriched with hydroxyapatite and silver nanoparticles for biomedical uses

Skin injuries are some of the most common problems faced by those with trouble healing. Medicine currently searches for multifunctional biomaterials that can enhance healing, while providing surface features favorable to human skin and unfavorable to microorganisms. In this context, this work aims to produce natural rubber latex (NRL) dressings enriched with hydroxyapatite - Ca10(PO4)6(OH)2 - and silver nanoparticles through magnetron sputtering. These dressings are provided with specific properties such as wettability, roughness and bacteriostatic activity to prevent cell adhesion and allow tissue regeneration without contamination by microorganisms. Modified NRL films showed hydrophilic character, along with an increase in roughness and Ca/P molar ratio of 0.7. The rate of fluid absorption of the films with (phosphate-buffered saline) solution demonstrates that the dressings will retain a certain amount of exudate. Also, silver, which is most likely in the form of nanoclusters, was leached in a proper quantity into a fluid medium. Biological assays proved that the dressings did not present cytotoxic effects in contact with fibroblasts and displayed bacteriostatic activity against S. aureus and E. coli. Fibroblast cells did not adhere over the samples, but proliferation was improved with time. This work successfully joined the benefits of calcium phosphate with silver-enrichment against bacteria using surface engineering techniques on the modification of NRL. Ultimately, the dressings produced in this study are promising for application in wound healing.

Cellulose-based composite scaffolds for bone tissue engineering and localized drug delivery.

Natural bone constitutes a complex and organized structure of organic and inorganic components with limited ability to regenerate and restore injured tissues, especially in large bone defects. To improve the reconstruction of the damaged bones, tissue engineering has been introduced as a promising alternative approach to the conventional therapeutic methods including surgical interventions using allograft and autograft implants. Bioengineered composite scaffolds consisting of multifunctional biomaterials in combination with the cells and bioactive therapeutic agents have great promise for bone repair and regeneration. Cellulose and its derivatives are renewable and biodegradable natural polymers that have shown promising potential in bone tissue engineering applications. Cellulose-based scaffolds possess numerous advantages attributed to their excellent properties of non-toxicity, biocompatibility, biodegradability, availability through renewable resources, and the low cost of preparation and processing. Furthermore, cellulose and its derivatives have been extensively used for delivering growth factors and antibiotics directly to the site of the impaired bone tissue to promote tissue repair. This review focuses on the various classifications of cellulose-based composite scaffolds utilized in localized bone drug delivery systems and bone regeneration, including cellulose-organic composites, cellulose-inorganic composites, cellulose-organic/inorganic composites. We will also highlight the physicochemical, mechanical, and biological properties of the different cellulose-based scaffolds for bone tissue engineering applications.

Engineering multifunctional bioactive citrate-based biomaterials for tissue engineering.

Developing bioactive biomaterials with highly controlled functions is crucial to enhancing their applications in regenerative medicine. Citrate-based polymers are the few bioactive polymer biomaterials used in biomedicine because of their facile synthesis, controllable structure, biocompatibility, biomimetic viscoelastic mechanical behavior, and functional groups available for modification. In recent years, various multifunctional designs and biomedical applications, including cardiovascular, orthopedic, muscle tissue, skin tissue, nerve and spinal cord, bioimaging, and drug or gene delivery based on citrate-based polymers, have been extensively studied, and many of them have good clinical application potential. In this review, we summarize recent progress in the multifunctional design and biomedical applications of citrate-based polymers. We also discuss the further development of multifunctional citrate-based polymers with tailored properties to meet the requirements of various biomedical applications.

One step preparation of multifunctional poly (ether sulfone) thin films with potential for wound dressing.

The increasing demand for higher-quality medical care has resulted in the obsolescence of traditional biomaterials. Medical care is currently transitioning from an era depending on single-functional biomaterials to one that is supported by multifunctional and stable biomaterials. Herein, long-lasting multifunctional poly(ether sulfone) thin films (MPFs) containing heparin-mimic groups and a quaternary ammonium compound (QAC) were prepared via semi-interpenetrating polymer network (SIPN) strategy. The MPFs, with rough surface and inner finger-like macrovoid, had better hydrophilicity and anti-protein fouling ability, as revealed by scanning electron microscopy (SEM), atomic force microscope (AFM) and water contact angle (WCA) and protein adsorption tests. The results of platelet adhesion and activation, and clotting time confirmed that the hemocompatibility of the MPFs was significantly improved. From cell culture and germ-culture test, it was noted that the overall trend of human umbilical vein endothelial cell (HUVEC) proliferation was enhanced by a combination of heparin-mimic groups and QAC, whereas the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was significantly prohibited. In addition, the MPFs were capable of modulating the expression level of basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-β1) in fibroblast, which was beneficial to controlling the formation of hypertrophic scar. In summary, the MPFs had potential to be used in the field of wound management and the study might help guide the design of surface structure of wound dressing.