Malate-Based Biodegradable Scaffolds Activate Cellular Energetic Metabolism for Accelerated Wound Healing.

The latest advancements in cellular bioenergetics have revealed the potential of transferring chemical energy to biological energy for therapeutic applications. Despite efforts, a three-dimensional (3D) scaffold that can induce long-term bioenergetic effects and facilitate tissue regeneration remains a big challenge. Herein, the cellular energetic metabolism promotion ability of l-malate, an important intermediate of the tricarboxylic acid (TCA) cycle, was proved, and a series of bioenergetic porous scaffolds were fabricated by synthesizing poly(diol l-malate) (PDoM) prepolymers via a facial one-pot polycondensation of l-malic acid and aliphatic diols, followed by scaffold fabrication and thermal-cross-linking. The degradation products of the developed PDoM scaffolds can regulate the metabolic microenvironment by entering mitochondria and participating in the TCA cycle to elevate intracellular adenosine triphosphate (ATP) levels, thus promoting the cellular biosynthesis, including the production of collagen type I (Col1a1), fibronectin 1 (Fn1), and actin alpha 2 (Acta2/α-Sma). The porous PDoM scaffold was demonstrated to support the growth of the cocultured mesenchymal stem cells (MSCs) and promote their secretion of bioactive molecules [such as vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), and basic fibroblast growth factor (bFGF)], and this stem cells-laden scaffold architecture was proved to accelerate wound healing in a critical full-thickness skin defect model on rats.

Anti-oxidant anti-inflammatory and antibacterial tannin-crosslinked citrate-based mussel-inspired bioadhesives facilitate scarless wound healing.

The revolutionary role of tissue adhesives in wound closure, tissue sealing, and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing. In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators (exemplified by sodium periodate and silver nitrate), herein, the natural polyphenolic compound tannic acid (TA) was used to achieve near instantaneous (<25s), hydrogen bond mediated gelation of citrate-based mussel-inspired bioadhesives combining anti-oxidant, anti-inflammatory, and antimicrobial activities (3A-TCMBAs). The resulting materials were self-healing and possessed low swelling ratios (<60%) as well as considerable mechanical strength (up to ∼1.0 MPa), elasticity (elongation ∼2700%), and adhesion (up to 40 kPa). The 3A-TCMBAs showed strong in vitro and in vivo anti-oxidant ability, favorable cytocompatibility and cell migration, as well as photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli (>90% bacterial death upon near-infrared (NIR) irradiation). In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs + NIR treatment could promote wound closure and collagen deposition and improve the collagen I/III ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines. Further, phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation & remodeling of the extracellular matrix (ECM) in the late stage (supported by phased CD31 (platelet endothelial cell adhesion molecule-1) PDGF (platelet-derived growth factor) and VEGF (vascular endothelial growth factor) expression as well as elevated matrix metalloprotein-9 (MMP-9) expression on day 21), resulting in scarless wound healing. The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant, new class of bioadhesive.

Recent Advances in the Development and Antimicrobial Applications of Metal-Phenolic Networks.

Due to the abuse of antibiotics and the emergence of multidrug resistant microorganisms, medical devices, and related biomaterials are at high risk of microbial infection during use, placing a heavy burden on patients and healthcare systems. Metal-phenolic networks (MPNs), an emerging organic-inorganic hybrid network system developed gradually in recent years, have exhibited excellent multifunctional properties such as anti-inflammatory, antioxidant, and antibacterial properties by making use of the coordination between phenolic ligands and metal ions. Further, MPNs have received widespread attention in antimicrobial infections due to their facile synthesis process, excellent biocompatibility, and excellent antimicrobial properties brought about by polyphenols and metal ions. In this review, different categories of biomaterials based on MPNs (nanoparticles, coatings, capsules, hydrogels) and their fabrication strategies are summarized, and recent research advances in their antimicrobial applications in biomedical fields (e.g., skin repair, bone regeneration, medical devices, etc.) are highlighted.

Functional Macromolecular Adhesives for Bone Fracture Healing.

Compared with traditional internal fixation devices, bone adhesives are expected to exhibit remarkable advantages, such as improved fixation of comminuted fractures and maintained spatial location of fractured scattered bone pieces in treating bone injuries. In this review, different bone adhesives are summarized from the aspects of bone tissue engineering, and the applications of bone adhesives are emphasized. The concepts of "liquid scaffold" and "liquid plate" are proposed to summarize two different research directions of bone adhesives. Furthermore, significant advances of bone adhesives in recent years in mechanical strength, osseointegration, osteoconductivity, and osteoinductivity are discussed. We conclude this topic by providing perspectives on the state-of-the-art research progress and future development trends of bone adhesives. We hope this review will provide a comprehensive summary of bone adhesives and inspire more extensive and in-depth research on this subject.

Citrate-based mussel-inspired magnesium whitlockite composite adhesives augmented bone-to-tendon healing.

Citrate-based mussel-inspired whitlockite composite adhesives (CMWAs) were developed and administered to the bone-tendon interface in anterior cruciate ligament (ACL) reconstruction. CMWAs could improve the initial bone-tendon bonding strength, promote the bony inward growth from the bone tunnel and enhance the chondrogenesis and osteogenesis of the bone-tendon interface, thus augmenting bone-to-tendon healing.

Facile Polyphenol-Europium Assembly Enabled Functional Poly(l-Lactic Acid) Nanofiber Mats with Enhanced Antioxidation and Angiogenesis for Accelerated Wound Healing.

Burns, trauma, surgery and chronic diabetic ulcers are the most common reasons causing skin wounds in clinic. Thus, developing a functional wound dressing has been an imperative issue. Herein, functional wound dressing (poly(l-lactic acid) PLLA-((tanic acid (TA)/europium (Eu))n ) is fabricated through a facile polyphenol-europium ion assembly to ameliorate wound microenvironment via scavenging excessive reactive oxygen species (ROS) and promoting angiogenesis. The physicochemical characterization indicates that the multicycle assembled TA/Eu is uniformly deposited on PLLA-(TA/Eu)n nanofiber mats surface. In vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant tests display good antioxidant ability by scavenging more than 75% ROS, and significantly increasing the antioxidant enzyme levels in vivo. Cytocompatibility experiments illustrate that PLLA-(TA/Eu)n nanofiber mats can promote the adhesion and proliferation of human umbilical vein endothelial cells (HUVECs) and L929 cells. Meanwhile, real-time quantitative polymerase chain reaction (PCR) (RT-qPCR) and western blot assays illustrate that it can stimulate proangiogenesis by elevating the expression of angiogenesis-related genes and proteins. In vivo Sprague-Dawley (SD) rats experiments indicate that PLLA-(TA/Eu)n nanofiber mats can significantly promote wound healing by improving both angiogenesis and antioxidant activity. Taken together, the functional PLLA-(TA/Eu)n nanofiber mats can offer significant promise as wound dressing for accelerated wound healing.

Platinum-crosslinking polymeric nanoparticle for synergetic chemoradiotherapy of nasopharyngeal carcinoma.

Despite extensive use of radiotherapy in nasopharyngeal carcinoma (NPC) treatment because of its high radiosensitivity, there have been huge challenges in further improving therapeutic effect, meanwhile obviously reducing radiation damage. To this end, synergistic chemoradiotherapy has emerged as a potential strategy for highly effective NPC therapy. Here, we developed RGD-targeted platinum-based nanoparticles (RGD-PtNPs, denoted as RPNs) to achieve targeted chemoradiotherapy for NPC. Such nanoparticles consist of an RGD-conjugated shell and a cis-platinum (CDDP) crosslinking core. Taking advantage of RGD, the RPNs may effectively accumulate in tumor, penetrate into tumor tissues and be taken by cancer cells, giving rise to a high delivery efficiency of CDDP. When they are fully enriched in tumor sites, the CDDP loaded RPNs can act as radiotherapy sensitizer and chemotherapy agents. By means of X-ray-promoted tumor cell uptake of nanoparticle and CDDP-induced cell cycle arrest in radiation-sensitive G2/M phases, RPNs may offer remarkable therapeutic outcome in the synergistic chemoradiotherapy for NPC.

TCP/PLGA composite scaffold loaded rapamycin in situ enhances lumbar fusion by regulating osteoblast and osteoclast activity.

The purpose of this study was to develop a novel ß-tricalcium phosphate (TCP)/poly (D,L-lactic-co-glycolic acid) (PLGA) composite scaffold loaded with rapamycin that can regulate the activity of osteoblasts and osteoclasts for lumbar fusion. The TCP/PLGA composite scaffold was fabricated by cryogenic three-dimensional printing techniques and then loaded with rapamycin in situ. The structural surface morphology of the composite scaffold was tested with scanning electron microscope. To evaluate the biocompatibility of the composite scaffold in vitro, bone marrow mesenchymal stem cells (BMSCs) were cultured on the TCP/PLGA composite scaffold slide and tested with Live/Dead Viability Kit. The effect of rapamycin on osteoclast and osteoblast was studied with staining and Western blotting. The in vitro results showed that the rapamycin-loaded TCP/PLGA composite scaffold showed good biocompatibility with BMSC and released rapamycin obviously promoted the osteoblast differentiation and mineralization. In vivo study, the TCP/PLGA composite scaffold loaded with rapamycin were implanted in lumbar fusion model and study with micro-computed tomography scanning, hematoxylin-eosin, Masson, and immune-histological staining, to evaluate the effect of rapamycin on bone fusion. The in vivo results demonstrated that rapamycin-loaded TCP/PLGA composite scaffold could enhance bone formation by regulating osteoblast and osteoclast activity, respectively. In this study, the TCP/PLGA composite scaffold loaded with rapamycin was confirmed to provide great compatibility and improved performance in lumbar fusion by regulating osteoblastic and osteoclastic activity and would be a promising composite biomaterial for bone tissue engineering.

Clinical application of polyurethane meniscal scaffold: A meta-analysis.

OBJECTIVE: In patients with partial meniscus defect, the implantation of polyurethane meniscal scaffold has become a common method for the treatment of meniscus vascular entry and tissue regeneration. However, it is unclear whether polyurethane meniscal scaffold will yield better clinical and MRI results after surgery. This meta-analysis compared the clinical and MRI results of polyurethane meniscal scaffold in some patients with meniscus defects. METHODS: By searching PubMed, Embase, and Cochrane Library, a systematic review of studies evaluating the clinical outcomes of patients with polyurethane meniscal scaffold implantation. The search terms used are: "meniscus", "meniscal", "scaffold", "Actifit" "polyurethane" and "implant". The study was evaluated based on the patient's reported outcome score, accompanying surgery, and radiology results. Genovese scale was used to evaluate morphology and signal intensity, and Yulish score was used to evaluate the imaging performance of articular cartilage. RESULTS: There were 16 studies that met the inclusion criteria, a total of 613 patients, and the overall average follow-up time was 41 months. The clinical scores at the final follow-up, such as VAS, IKDC, Tegner, and KOOS, were significantly improved compared with preoperatively. The MS, SI, and IIRMC scores evaluated in MRI showed no significant difference between preoperative and final follow-up. However, for AC (OR 0.34, 95% CI 0.11-1.00; P = 0.05) and AME (OR 0.08, 95% CI 0.03-0.22; P < 0.01), the final follow-up results were worse than preoperatively. CONCLUSIONS: This meta-analysis found that compared with preoperative, the clinical effect of the final follow-up was significantly improved. However, MS, SI, and IIRMC in MRI parameters did not change significantly. In addition, the final follow-up results of AC and AME showed a deteriorating trend. Therefore, for patients with partial meniscus defects, polyurethane meniscal scaffold seem to be a viable option, and further research is needed to determine whether the deterioration of AC and AME is clinically relevant.

Magnesium oxide-crosslinked low-swelling citrate-based mussel-inspired tissue adhesives.

Tissue adhesives are commonly used in surgeries and regenerative engineering for the repair and regeneration of topical and internal wounds on tissues and organs such as skin, heart, blood vessels, and bone. However, achieving rapid crosslinking, strong wet adhesion and cohesion strengths, and minimal cytotoxicity remains a critical roadblock for clinical translation. Herein, in contrast to harsh and cytotoxic oxidants, magnesium oxide (MgO) particles were found to facilitate rapid crosslinking for injectable citrate-based mussel-inspired tissue bioadhesives synthesized by reacting citric acid, PEG-PPG-PEG diol and dopamine (iC-EPE). Our results confirmed the role of MgO particles as both crosslinkers and composite fillers to concurrently enhance bioadhesive cohesion and adhesion. iC-EPE crosslinked by MgO with/without sodium periodate (PI) exhibit enhanced mechanical strengths (1.0 Mpa < tensile strength ≤ 4.5 MPa) compared to that of iC-EPE crosslinked only by PI (~0.75 MPa), high adhesion strength (up to 125 kPa, 8 fold that of fibrin glue (~15 kPa)), tunable degradability (full degradation from <1 week to > 1 month), excellent in vitro and in vivo biocompatibility, encouraging anti-bacterial performance, and favorable wound closure efficacy. Thus, MgO crosslinked bioadhesives possess great potential for a wide range of applications in surgery and regenerative engineering.

Light-Activatable Prodrug and AIEgen Copolymer Nanoparticle for Dual-Drug Monitoring and Combination Therapy.

Polyprodrug nanoparticles have been employed recently for safer and more effective cancer treatment. However, it remains a challenge to elucidate how and when the polyprodrug nanoparticles are dissociated and activated to release active drugs in cancer cells. Herein, a visible light-activatable Pt(IV) prodrug and an aggregation-induced emission luminogen (AIEgen) were copolymerized and embedded in the main chain of PtAIECP, and the chemotherapeutic doxorubicin (DOX) was subsequently encapsulated in the nanoparticles self-assembled by PtAIECP (PtAIECP@DOX NP). PtAIECP@DOX NP enabled the monitoring of both the light-activation of Pt(IV) prodrug to active Pt(II) and release of encapsulated DOX intracellularly through the fluorescence "turn-on" in the course of visible-light-induced polymer-main-chain cleavage and self-assembled structure dissociation in vitro and ex vivo. The synergistic anticancer efficacy of the activated Pt(II) drug and DOX in PtAIECP@DOX NP was also investigated in vitro and in vivo. The implementation of polyprodrug and AIE combination strategy empowered dual drug release and monitoring, which could be further used to guide the temporal and spatial control of light irradiation to maximize therapeutic efficiency, and will inspire other combinational bioimaging and therapy strategies.

Development of Organic/Inorganic Compatible and Sustainably Bioactive Composites for Effective Bone Regeneration.

In this paper, we demonstrate a strategy of covalently bonding bioactive molecules onto inorganic hydroxyapatite (HAp) to improve the compatibility between organic and inorganic components and endow the bone composites with sustainable bioactivity. Bone morphogenetic protein-2 (BMP-2) peptide covalently immobilized nano-hydroxyapatite (nHAp-BMP-2) is developed to preserve the bioactivity and slow the release of the BMP-2 peptide. Then nHAp-BMP-2 was further incorporated into an ultraviolet-curable mixture of gelatin methacrylamide (GelMA) and four-armed PEG methacrylamide (four-armed PEGMA) to form a Gel/(nHAp-BMP-2) composite. The hydrogen bonding between gelatin and BMP-2 on nHAp-BMP-2 enhanced the compatibility between inorganic and organic components. The Gel/(nHAp-BMP-2) composite exhibited superior biocompatibility caused by gelatin and nHAp-BMP-2, except in a two-dimensional cell culture, the hydrogel was also capable of a three-dimensional cell culture. In addition, the introduction of nHAp-BMP-2 had a positive influence on bone marrow mesenchymal stem cell proliferation, differentiation, and the subsequent calcification on the composite. After treatment of a rat calvarial defect model for 12 weeks, the Gel/(nHAp-BMP-2) group showed the largest new bone volume and the highest ratio of new bone (50.54 ± 13.51 mm3 and 64.38 ± 17.22%, respectively) compared to those of the other groups. These results demonstrate that this way of controlling BMP-2 release is effective and the Gel/(nHAp-BMP-2) composite has great potential in bone regeneration therapy.

The critical chemical and mechanical regulation of folic acid on neural engineering.

The mandate of folic acid supplementation in grained products has reduced the occurrence of neural tube defects by one third in the U.S since its introduction by the Food and Drug Administration in 1998. However, the advantages and possible mechanisms of action of using folic acid for peripheral nerve engineering and neurological diseases still remain largely elusive. Herein, folic acid is described as an inexpensive and multifunctional niche component that modulates behaviors in different cells in the nervous system. The multiple benefits of modulation include: 1) generating chemotactic responses on glial cells, 2) inducing neurotrophin release, and 3) stimulating neuronal differentiation of a PC-12 cell system. For the first time, folic acid is also shown to enhance cellular force generation and global methylation in the PC-12 cells, thereby enabling both biomechanical and biochemical pathways to regulate neuron differentiation. These findings are evaluated in vivo for clinical translation. Our results suggest that folic acid-nerve guidance conduits may offer significant benefits as a low-cost, off-the-shelf product for reaching the functional recovery seen with autografts in large sciatic nerve defects. Consequently, folic acid holds great potential as a critical and convenient therapeutic intervention for neural engineering, regenerative medicine, medical prosthetics, and drug delivery.

Development of tannin-inspired antimicrobial bioadhesives.

Tissue adhesives play an important role in surgery to close wounds, seal tissues, and stop bleeding, but existing adhesives are costly, cytotoxic, or bond weakly to tissue. Inspired by the water-resistant adhesion of plant-derived tannins, we herein report a new family of bioadhesives derived from a facile, one-step Michael addition of tannic acid and gelatin under oxidizing conditions and crosslinked by silver nitrate. The oxidized polyphenol groups of tannic acid enable wet tissue adhesion through catecholamine-like chemistry, while both tannic acid and silver nanoparticles reduced from silver nitrate provide antimicrobial sources inherent within the polymeric network. These tannin-inspired gelatin bioadhesives are low-cost and readily scalable and eliminate the concerns of potential neurological effect brought by mussel-inspired strategy due to the inclusion of dopamine; variations in gelatin source (fish, bovine, or porcine) and tannic acid feeding ratios resulted in tunable gelation times (36 s-8 min), controllable degradation (up to 100% degradation within a month), considerable wet tissue adhesion strengths (up to 3.7 times to that of fibrin glue), excellent cytocompatibility, as well as antibacterial and antifungal properties. The innate properties of tannic acid as a natural phenolic crosslinker, molecular glue, and antimicrobial agent warrant a unique and significant approach to bioadhesive design. STATEMENT OF SIGNIFICANCE: This manuscript describes the development of a new family of tannin-inspired antimicrobial bioadhesives derived from a facile, one-step Michael addition of tannic acid and gelatin under oxidizing conditions and crosslinked by silver nitrate. Our strategy is new and can be easily extended to other polymer systems, low-cost and readily scalable, and eliminate the concerns of potential neurological effect brought by mussel-inspired strategy due to the inclusion of dopamine. The tannin-inspired gelatin bioadhesives hold great promise for a number of applications in wound closure, tissue sealant, hemostasis, antimicrobial and cell/drug delivery, and would be interested to the readers from biomaterials, tissue engineering, and drug delivery area.

Development of Citrate-based Dual-Imaging Enabled Biodegradable Electroactive Polymers.

Increasing occurrences of degenerative diseases, defective tissues and severe cancers heighten the importance of advanced biomedical treatments, which in turn enhance the need for improved biomaterials with versatile theranostic functionalities yet using minimal design complexity. Leveraging the advantages of citrate chemistry, we developed a multifunctional citrate-based biomaterial platform with both imaging and therapeutic capabilities utilizing a facile and efficient one-pot synthesis. The resulting aniline tetramer doped biodegradable photoluminescent polymers (BPLPATs) not only possess programmable degradation profiles (<1 to >6 months) and mechanical strengths (~20 MPa to > 400 MPa), but also present a combination of intrinsic fluorescence, photoacoustic (PA) and electrical conductivity properties. BPLPAT nanoparticles are able to label cells for fluorescence imaging and perform deep tissue detection with PA imaging. Coupled with significant photothermal performance, BPLPAT nanoparticles demonstrate great potential for thermal treatment and in vivo real-time detection of cancers. Our results on BPLPAT scaffolds demonstrate three-dimensional (3D) high-spatial-resolution deep tissue PA imaging (23 mm), as well as promote growth and differentiation of PC-12 nerve cells. We envision that the biodegradable dual-imaging-enabled electroactive citrate-based biomaterial platform will expand the currently available theranostic material systems and open new avenues for diversified biomedical and biological applications via the demonstrated multi-functionality.

Simultaneously Photo-Cleavable and Activatable Prodrug-Backboned Block Copolymer Micelles for Precise Anticancer Drug Delivery.

A simultaneously photo-cleavable and activatable prodrug-backboned block copolymer (BCP) micelle strategy is demonstrated. Without light treatment, the micelles stay silent and inactivated, being biocompatible to normal tissues. Concurrent chain cleavage of BCP micelles and the activation of Pt(IV) prodrug could be temporally and spatially triggered by UV or even visible light for precise anticancer drug delivery.

Click Cross-Linking-Improved Waterborne Polymers for Environment-Friendly Coatings and Adhesives.

Waterborne polymers, including waterborne polyurethanes (WPU), polyester dispersions (PED), and polyacrylate emulsions (PAE), are employed as environmentally friendly water-based coatings and adhesives. An efficient, fast, stable, and safe cross-linking strategy is always desirable to impart waterborne polymers with improved mechanical properties and water/solvent/thermal and abrasion resistance. For the first time, click chemistry was introduced into waterborne polymer systems as a cross-linking strategy. Click cross-linking rendered waterborne polymer films with significantly improved tensile strength, hardness, adhesion strength, and water/solvent resistance compared to traditional waterborne polymer films. For example, click cross-linked WPU (WPU-click) has dramatically improved the mechanical strength (tensile strength increased from 0.43 to 6.47 MPa, and Young's modulus increased from 3 to 40 MPa), hardness (increased from 59 to 73.1 MPa), and water resistance (water absorption percentage dropped from 200% to less than 20%); click cross-linked PED (PED-click) film also possessed more than 3 times higher tensile strength (∼28 MPa) than that of normal PED (∼8 MPa). The adhesion strength of click cross-linked PAE (PAE-click) to polypropylene (PP) was also improved (from 3 to 5.5 MPa). In addition, extra click groups can be preserved after click cross-linking for further functionalization of the waterborne polymeric coatings/adhesives. In this work, we have demonstrated that click modification could serve as a convenient and powerful approach to significantly improve the performance of a variety of traditional coatings and adhesives.

Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives.

Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern.

Fast degradable citrate-based bone scaffold promotes spinal fusion.

It is well known that high rates of fusion failure and pseudoarthrosis development (5~35%) are concomitant in spinal fusion surgery, which was ascribed to the shortage of suitable materials for bone regeneration. Citrate was recently recognized to play an indispensable role in enhancing osteconductivity and osteoinductivity, and promoting bone formation. To address the material challenges in spinal fusion surgery, we have synthesized mechanically robust and fast degrading citrate-based polymers by incorporating N-methyldiethanolamine (MDEA) into clickable poly(1, 8-octanediol citrates) (POC-click), referred to as POC-M-click. The obtained POC-M-click were fabricated into POC-M-click-HA matchstick scaffolds by compositing with hydroxyapatite (HA) for interbody spinal fusion in a rabbit model. Spinal fusion was analyzed by radiography, manual palpation, biomechanical testing, and histological evaluation. At 4 and 8 weeks post surgery, POC-M-click-HA scaffolds presented optimal degradation rates that facilitated faster new bone formation and higher spinal fusion rates (11.2±3.7, 80±4.5 at week 4 and 8, respectively) than the poly(L-lactic acid)-HA (PLLA-HA) control group (9.3±2.4 and 71.1±4.4) (p<0.05). The POC-M-click-HA scaffold-fused vertebrates possessed a maximum load and stiffness of 880.8±14.5 N and 843.2±22.4 N/mm, respectively, which were also much higher than those of the PLLA-HA group (maximum: 712.0±37.5 N, stiffness: 622.5±28.4 N/mm, p<0.05). Overall, the results suggest that POC-M-click-HA scaffolds could potentially serve as promising bone grafts for spinal fusion applications.

Functionalized graphene oxide nanoparticles for cancer cell-specific delivery of antitumor drug.

The unique reduction-triggered functional graphene oxide nanoparticles (GON) with well-defined size and uniform distribution were designed as an innovative drug delivery platform for cancer treatment for the first time, via the redox radical polymerization of methacrylic acid from the polyethylene glycol (PEG) modified GON (GON-PEG), following by cross-linking with cystamine. Thermogravimetric analysis demonstrates that the typical PMAA2-GON-PEG carriers contain about 16 wt % PEG segments and 33 wt % poly(methacrylic acid) (PMAA) brushes. PEG moieties are incorporated to make the drug delivery platforms stealthy during blood circulation. Notably, introducing the cross-linked PMAA brushes efficiently minimizes the premature release of doxorubicin (DOX) in the stimulated normal tissues, and accelerates DOX release in the stimulated tumor tissues through response to reduce agent. The carriers showed a 6-fold faster releasing rate at pH 5.0 in the presence of 10 mM glutathione (GSH) (stimulated tumor tissues) than at pH 7.4 with 10 µM GSH (stimulated normal tissues). In vitro cytotoxicity test also showed that the cross-linked PMAA2-GON-PEG (CPMAA2-GON-PEG) carriers had remarkable cytocompatibility, and that the DOX-loaded CPMAA2-GON-PEG had excellent killing capability to SiHa cells.