Magnesium (Mg) and its alloys have been intensively explored as the next generation of metallic bone substitutes in past decades, but their rapid corrosion rate in physiological environments is still a great hindrance for further therapeutic applications. In the present study, we attempt to design biodegradable poly(L-lactic acid) (PLLA) coatings on pure Mg substrates (99.99 wt %) with tunable surface morphologies through dip-coating in combination with mixed nonsolvent induced phase separation (Dip-coating-mNIPS) method to regulate their corrosion behavior and biocompatibility. We applied the mixtures of ethanol and hexane as the coagulation baths, and changed the composition of mixed nonsolvent and the concentration of polymer solution to obtain PLLA coatings with different pore sizes and morphologies. Standard electrochemical measurements and immersion tests demonstrated that all PLLA coatings could effectively enhance the corrosion resistance of Mg substrates but that the corrosion behaviors varied among coatings with different surface and inner structures. A systematic investigation of cellular response through MTT assay, LIVE/DEAD staining, cell distribution, and cell attachment indicated that PLLA-coated Mg substrates could enhance cytocompatibility in comparison to pure Mg. In addition, the cellular behaviors were affected by the corrosion activity as well as the surface properties of different PLLA coatings. Our findings illustrated that through the Dip-coating-mNIPS method, the structure of the PLLA membrane on Mg substrates could easily be controlled to regulate the corrosion behaviors and further improve the biocompatibility. This presents great potential in designing functional polymer coatings on Mg-based orthopedic implants to meet specific clinical requirements.

Although numerous studies have been conducted to describe the gelation of multi-arm star polymers, reports on the relationship among rheological quantities, overlap concentration (c*), and microstructures have still remained insufficient. Here, we examine the sol–gel dynamics of hydrogels formed by 4-arm poly­(ethylene glycol) (PEG) near c* based on dynamic scaling theory. We investigated the evolution of viscoelastic modulus (storage modulus G′ and loss modulus G″) with reduced gelation time (τ) and the normalized extent of crosslinking (ϵ), and a divergent dependence was observed near c*. A general expression of the Hill equation was employed to evaluate the complex modulus spectra and critical relaxation exponent (Δ) at the gel point (i.e., G′ ∼ G″ ∼ ωΔ), providing a way to access such a critical exponent, regardless of how fast the gelation occurs. Besides, the dynamic scaling exponent with ϵ shows high sensitivity to the pre-gel clusters and post-gel networks. Moreover, two-dimensional time–frequency viscoelastic mapping indicates that the hydrogel formed at c* shows higher homogeneity than those away from c*, and inhomogeneity of the local cluster density would contribute to the large-scale fluctuation in rheological quantities during gelation.

Nowadays, the need for bio‐implants, which can gradually degrade after fulfilling the therapeutic tasks is continuously increasing. Under such situation, magnesium (Mg) and its alloys have been proposed and intensively studied as the new‐generation medical implants due to their favorable biodegradability and biocompatibility. However, their swift corrosion in physiological environments can always cause an early fracture and further the surgical failure, greatly hindering their broad applications. Therefore, great efforts have been made to alter the degradation behaviors of Mg‐based implants. Biodegradable polymeric surface coatings have been revealed to be a straightforward and effective strategy for retarding the fast degradation and improving the bioactivity of Mg and its alloys. This article reviews the recent progress of polymer‐based coatings on Mg substrates, regarding the coating strategies, coating properties, and their performance in corrosive protection and biocompatibility promotion via in vitro as well as some in vivo models. The specific pros and cons of different polymeric coatings are also discussed. Finally, we put forward some perspectives on the future direction of polymeric coatings on biomedical Mg‐based implants to better adapt to clinical trials.

Introduction Magnesium (Mg) has a prophylactic potential against the onset of hyperlipidemia. Similar to statin, Mg is recommended as lipid-lowering medication for hypercholesterolemia and concomitantly exhibits an association with increased bone mass. The combination of statin with Mg ions (Mg 2+ ) may be able to alleviate the high-fat diet (HFD)-induced bone loss and reduce the side-effects of statin. This study aimed to explore the feasibility of combined Mg 2+ with simvastatin (SIM) for treating HFD-induced bone loss in mice and the involving mechanisms. Materials and methods C57BL/6 male mice were fed with a HFD or a normal-fat diet (NFD). Mice were intraperitoneally injected SIM and/or orally received water with additional Mg 2+ until sacrificed. Enzyme-linked immunosorbent assay was performed to measure cytokines and cholesterol in serum and liver lysates. Bone mineral density (BMD) and microarchitecture were assessed by micro-computed tomography (μCT) in different groups. The adipogenesis in palmitate pre-treated HepG2 cells was performed under various treatments. Results μCT analysis showed that the trabecular bone mass was significantly lower in the HFD-fed group than that in NFD-fed group since week 8. The cortical thickness in HFD-fed group had a significant decrease at week 24, as compared with NFD-fed group. The combination of Mg 2+ and SIM significantly attenuated the trabecular bone loss in HFD-fed mice via arresting the osteoclast formation and bone resorption. Besides, such combination also reduced the hepatocytic synthesis of cholesterol and inhibited matrix metallopeptidase 13 ( Mmp13 ) mRNA expression in pre-osteoclasts. Conclusions The combination of Mg 2+ and SIM shows a synergistic effect on attenuating the HFD-induced bone loss. Our current formulation may be a cost-effective alternative treatment to be indicated for obesity-related bone loss.

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Magnesium (Mg) and its alloys show excellent potential as orthopedic implantable materials, with their in vivo degraded Mg ions (Mg 2+ ) known to promote the growth of new bone. However, the swift corrosion process during implantation has greatly hindered its clinical applications. A method to counter the high rate of corrosion is to coat Mg substrates on surfaces with a thin layer of biodegradable polymer. Although such a coating reduces the long-term corrosion rate, it also prevents the shortterm release of bone-simulating Mg 2+ after orthopedic operations. To balance these contradicting short-and long-term characteristics, we present a polymer−inorganic composite coating on pure Mg substrates that enables Mg-based implants to achieve controllable release of Mg 2+ and high corrosion resistance simultaneously. The coatings were fabricated by adding an appropriate amount of inorganic magnesium sulfate heptahydrate (MgSO 4 •7H 2 O) salt particles into a biodegradable poly(L-lactic acid) (PLLA) polymer matrix, such that they can percolate inside to form an interconnected morphology during the phase separation between Mg salt and PLLA polymers as solvent evaporates during the drying process, resulting in the formation of an organic−inorganic composite coating. The in vitro corrosion tests indicated that the composite coatings with lower Mg salt loading had the best degradation behavior, resulting in controllable release of Mg 2+ and alkaline shift. Cytocompatibility of bare and coated Mg were investigated via MC3T3-E1 preosteoblasts through MTT assay and LIVE/DEAD imaging, along with the observation of cell distribution and adhesion behaviors. The results further demonstrated that the incorporation of a suitable amount of Mg salt particles could further improve the cytocompatibility as compared to the pristine PLLA coating. We believe such fabricated organic−inorganic composite coatings could have great potential for application on Mg substrates to obtain Mg-based biomaterials with higher practical value in clinical treatments. KEYWORDS: PLLA/MgSO 4 •7H 2 O composite coating, biodegradable pure magnesium, controllable Mg 2+ release, high corrosion resistance, orthopedic implants

Guided bone regeneration (GBR) technique using a barrier membrane holds great potential to allow the single-stage reconstruction of critical-sized bone defects. Here, bioactive nanoneedle-like magnesium oxychloride ceramics (MOCs) are synthesized and recruited as an osteoinductive factor within a polycaprolactone-gelatin A (PCL-GelA) membranous matrix to generate a periosteum-mimicking biphasic GBR membrane (PCL-GelA/MOC) to accelerate calvarial defect repair. The PCL-GelA/MOC membrane acts as a shield for defect areas and a reservoir of osteoinductive molecules, which provides a favorable microenvironment for supporting cell proliferation, infiltration, and differentiation. This membrane leads to accelerated osteogenesis and angiogenesis, effectual defect bridging, and significantly enhanced bone regeneration when applied to a 5 mm sized rat calvarial defect. This makes this innovative and multifunctional GBR membrane a suitable candidate for clinical applications with promising curative efficacy.

Guided bone regeneration (GBR) therapy demonstrates a prominent curative effect on the management of craniomaxillofacial (CMF) bone defects. In this study, a GBR membrane consisting of a microporous layer and a struvite‐nanowire‐doped fibrous layer is constructed via non‐solvent induced phase separation, followed by an electrospinning procedure to treat critical‐sized calvarial defects. The microporous layer shows selective permeability for excluding the rapid‐growing non‐osteogenic tissues and potential wound stabilization. The nanowire‐like struvite is synthesized as the deliverable therapeutic agent within the fibrous layer to facilitate bone regeneration. Such a membrane displays a well‐developed heterogeneous architecture, satisfactory mechanical performance, and long‐lasting characteristics. The in vitro biological evaluation reveals that apart from being a strong barrier, the bilayer struvite‐laden membrane can actively promote cellular adhesion, proliferation, and osteogenic differentiation. Consequently, the multifunctional struvite‐doped membranes are applied to treat 5 mm‐sized bilateral calvarial defects in rats, resulting in overall improved healing outcomes compared with the untreated or the struvite‐free membrane‐treated group, which is characterized by enhanced osteogenesis and significantly increased new bone formation. The encouraging preclinical results reveal the great potential of the bilayer struvite‐doped membrane as a clinical GBR device for augmenting large‐area CMF bone reconstruction.