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Osteonecrosis, which is typically induced by trauma, glucocorticoid abuse, or alcoholism, is one of the most severe diseases in clinical orthopedics. Osteonecrosis often leads to joint destruction, and arthroplasty is eventually required. Enhancement of bone regeneration is a critical management strategy employed in osteonecrosis therapy. Bone tissue engineering based on engineered three-dimensional (3D) scaffolds with appropriate architecture and osteoconductive activity, alone or functionalized with bioactive factors, have been developed to enhance bone regeneration in osteonecrosis. In this review, we elaborate on the ideal properties of 3D scaffolds for enhanced bone regeneration in osteonecrosis, including biocompatibility, degradability, porosity, and mechanical performance. In addition, we summarize the development of 3D scaffolds alone or functionalized with bioactive factors for accelerating bone regeneration in osteonecrosis and discuss their prospects for translation to clinical practice., Graphical abstract Image 1, Highlights • Engineered three-dimensional scaffolds boost bone regeneration in osteonecrosis. • The ideal properties of three-dimensional scaffolds for osteonecrosis treatment are discussed. • Bioactive factors-functionalized three-dimensional scaffolds are promising bone regeneration devices for osteonecrosis management. • The challenges and opportunities of engineered three-dimensional scaffolds for osteonecrosis therapy are predicted.

Osteoporosis leads to various complications, such as prosthesis loosening and periprosthetic fracture, after joint replacement. This is mainly due to the impaired osteogenesis and excessive osteoclastic activity in osteoporotic microenvironment, which leads to insufficient osseointegration between prostheses and host bone. In this study, a functional drug-releasing inorganic-organic bioactive interface was constructed, comprising inorganic three-dimensional (3D) printed porous titanium alloy interface and organic poloxamer 407 temperature-sensitive hydrogel loaded with a novel anti-osteoporosis drug (technetium methylenediphosphonate, 99Tc-MDP). The inorganic-organic bioactive interface showed good biocompatibility and exhibited a sustained release profile. This performance enhanced osteogenic differentiation, inhibited the expression of osteoclast-related genes and inhibited the osteoclastogenesis, as compared with traditional bisphosphonates (alendronate) in vitro. When implanted into the distal femoral defect using an osteoporotic rabbit model, the 99Tc-MDP-loaded bioactive interface exhibited the most stable osseointegration with native bone. Furthermore, the drug delivery system inhibited osteoclastic activity via regulation of the osteoprotegerin/receptor activator of NF-κB ligand (OPG/RANKL) signaling pathway, which significantly ameliorated the osteoporosis status to effectively prevent continuous bone destruction around the interface. This study has clinical significance, as it demonstrates that the 99Tc-MDP modified inorganic-organic interface serve as a novel artificial prosthetic interface for patients with poor osteogenesis.

Local drug delivery systems composed of biomaterials and osteogenic substances provide promising strategies for the reconstruction of large bone defects. In recent years, simvastatin has been studied extensively for its pleiotropic effects other than lowering of cholesterol, including its ability to induce osteogenesis and angiogenesis. Accordingly, several studies of simvastatin incorporated drug delivery systems have been performed to demonstrate the feasibility of such systems in enhancing bone regeneration. Therefore, this review explores the molecular mechanisms by which simvastatin affects bone metabolism and angiogenesis. The simvastatin concentrations that promote osteogenic differentiation are analyzed. Furthermore, we summarize and discuss a variety of simvastatin-loaded drug delivery systems that use different loading methods and materials. Finally, current shortcomings of and future development directions for simvastatin-loaded drug delivery systems are summarized. This review provides various advanced design strategies for simvastatin-incorporated drug delivery systems that can enhance bone regeneration.

Patients with osteoporosis are more likely to suffer prosthesis displacement, subsidence or periprosthesis fracture after prosthesis replacement. This is due to excessive osteoclast activity and a lack of bone marrow mesenchymal stem cell (BMSC) integration at the implant-bone interface locally in the setting of osteoporosis. In order to inhibit local excessive bone resorption and promote bone integration, we have constructed a porous titanium/poloxamer 407 hydrogel system loaded with zoledronate (ZOL), a bisphosphonate, to promote osteointegration in a rabbit model of osteoporosis. This composite scaffold (ZOL/gTi) showed good biocompatibility and sustained ZOL release along with the degradation of hydrogel. Not only does this system provide a three-dimensional structural network for BMSC proliferation but also locally released ZOL promotes proliferation and osteogenic differentiation while inhibiting osteoclast differentiation of BMSCs in vitro. After implantation of ZOL/gTi into a distal femoral defect in the rabbits, micro-CT, histological, push-out, as well as genetic and protein analyses revealed significant promotion of osteointegration with the aid of this composite scaffold. Here, we provide an important theoretical basis for the research and development of bioactive implant interfaces for patients with osteogenic defects, such as osteoporosis. Keywords: Bioactive interface, Zoledronate, Osteoporotic microenvironment, Osseointegration

Hybrid two-dimensional (2D) van der Waals (vdW) p–n junctions are attractive due to the controlled synthesis of the physical performances of organic semiconductors and quantum confinement effects of 2D materials, enabling highly tunable optoelectronic performances as well as low-cost processability. Here, hybrid 2D heterostructures are fabricated using a p-type semiconducting polymer (PDVT-10) and n-type MoS2. An ultra-thin film (∼9 nm) of the PDVT-10 polymer is formed using the Langmuir–Schaefer (LS) technique. Large-scale MoS2 monolayers are prepared using a chemical vapor deposition (CVD) method. The PDVT-10/MoS2 vertical heterojunction devices show ambipolar charge transport properties with a p-type maximum field-effect mobility of 0.3 cm2 V−1 s−1 and an n-type maximum field-effect mobility of 2.45 cm2 V−1 s−1. In addition, the heterojunctions exhibit a great photoresponse under white light as well as a clear rectifying behavior.

A graphene-like coordination polymer based on copper(II) benzenehexathiol (Cu-BHT, 1) with high electric conductivity (103 S·cm–1) was prepared recently. The high conductivity makes this material a good candidate for electrocatalysis, and here its catalytic activity toward hydrogen evolution reaction (HER) was evaluated. Cu-BHT shows good activity and stability for HER in acidic solutions under high current densities. By changing the preparation conditions, the morphology of Cu-BHT materials was controlled at the mesoscale, which allows the preparation of a thin film (TF-1), nanocrystal (NC-1), and amorphous nanoparticle (NP-1) of Cu-BHT. The overpotential of Cu-BHT toward HER shows an improved activity from 760 mV (NC-1) to 450 mV (NP-1) at a current density of 10 mA·cm–2. A Tafel slope of ∼95 mV·dec–1 and an exchange current density of 10–3 mA·cm–2 were achieved under optimized conditions. Density functional theory calculations suggest that the “Cu-edge site” on the (100) surface plays an important role...

Conjugated backbones play a fundamental role in determining the electronic properties of organic semiconductors. On the basis of two solution-processable dihydropyrrolo[3,4-c]pyrrole-1,4-diylidenebis(thieno[3,2-b]thiophene) derivatives with aromatic and quinoid structures, we have carried out a systematic study of the relationship between the conjugated-backbone structure and the thermoelectric properties. In particular, a combination of UV–vis–NIR spectra, photoemission spectroscopy, and doping optimization are utilized to probe the interplay between energy levels, chemical doping, and thermoelectric performance. We found that a moderate change in the conjugated backbone leads to varied doping mechanisms and contributes to dramatic changes in the thermoelectric performance. Notably, the chemically doped A-DCV-DPPTT, a small molecule with aromatic structure, exhibits an electrical conductivity of 5.3 S cm–1 and a high power factor (PF373 K) up to 236 μW m–1 K–2, which is 50 times higher than that of Q-DCM...

Bone nonunion has become one of the most severe sequelae of fractures, infections, bone tumors, or revision arthroplasty owing to its high morbidity and disability rate. Recently, bone nonunion has received considerable attention from plastic surgeons. There are different treatment methods for nonunion depending on its classification according to the etiology and pathological types. Bone tissue engineering provides advanced platforms for the treatment of bone nonunion via the use of material scaffolds with sufficient mechanical strength. Meanwhile, it promotes bone regeneration and osseointegration by the addition of various growth factors or drugs. This review describes in detail the classification and leading causes of nonunion, as well as the clinical treatment methods and basic research progress, including the design of metal and bioactive material scaffolds. Future challenges in engineering, material science, and three-dimensional printing are also summarized. This article may provide new perspectives of the clinical translation for the treatment of bone nonunion by understanding the pathogenic mechanism and the rational application of bioactive scaffolds. Keywords: Material, Bone nonunion, Classification, Pathological feature, Treatment progress

The local sustained release of bioactive substances are attracting increasing attention in bone tissue engineering, which is beneficial to bone tissue formation and helps to improve the bone ingrowth ability of a scaffold. Bisphosphonates (BPs), as a representative kind of osteoclast inhibitors, are proven to possess excellent osteogenic induction capability. Accordingly, various physical and chemical strategies are developed to functionalize bone tissue scaffolds with BPs to achieve controlled release profiles. Compared with traditional treatment modalities, local release of BPs from these composite scaffolds will contribute to continuous bone integration without the risk of many complications. This review explores the molecular mechanisms of BPs on bone metabolism and analyzes the appropriate concentrations of BPs that promote bone regeneration. The advanced BP loading strategies, implant modification technologies, and BP-loaded composite scaffolds based on different matrices are summarized. Finally, the latest advances and the future development of BP-modified scaffolds for enhanced bone regeneration are discussed. This article provides leading-edge design strategies of the BP-functionalized bone engineering scaffolds for improved bone repairability.

Summary In the latest decade, two-dimensional (2D) π-d conjugated metal organic frameworks (MOFs) constructed from metal ions with square-planar coordination geometry and benzene- or triphenylene-derived ligands with ortho-disubstituted N, O, or S donor atoms have received great research interests because of their exceptional physical properties and promising applications. New MOFs of this class are constantly being reported, but 2D metal bis(diselenolene) MOFs based on organic ligands with ortho-disubstituted Se donor atoms have not been synthesized. Herein, a Lewis-acid-induced dealkylation protocol is introduced to the synthesis of arenepolyselenols and related coordination polymers. A triphenylene-derived diselenaborole compound is synthesized and employed as precursor reagent for the synthesis of 2,3,6,7,10,11-triphenylenehexaselenol (H6TPHS) and the first conductive metal organic framework namely Co-TPHS based on triphenylenehexaselenolate (TPHS6−). Co-TPHS exhibits porous honeycomb 2D structure and electrically conductive and glassy magnetic properties., Graphical Abstract, Highlights • A BBr3-induced dealkylation protocol is used to synthesize arenepolyselenols ligands • Triphenylenehexaselenol (TPHS) and a Co-TPHS MOF were synthesized for the first time • The MOF exhibits electrically conductive and glassy magnetic properties, Subject Areas: Chemical Synthesis; Magnetic Property; Polymers

Background Bone defects represent a common orthopedic condition. With its vast array of donor sources, xenogeneic bone shows considerable potential as a bone defect repair material but may also be associated with immune rejection and reduced osteogenic capacity. Thus, reducing the risks for immune rejection of xenogeneic bone, while improving its osseointegration, are key technical challenges. Methods Decellularized bone matrix scaffolds (DBMs) were fabricated by thorough ultrasonic vibration and subjection to chemical biological agents to remove cells and proteins. The DBMs were then mixed with platelet-rich plasma (PRP) under negative pressure. Growth factor concentrations of PRP, as well as the microstructures and biomechanical properties of the system, were examined. Furthermore, osseointegration capacities in the critical-size radial defect rabbit model were verified. Results Complete decellularization of the scaffold and limited reductions in mechanical strength were observed. Moreover, the obtained PRP demonstrated various growth factors. Radiographic evaluation and histological analysis verified that more new bone formation occurred in the DBM mixed with PRP group at 6 and 12 weeks after implantation compared with both the blank group and the DBM without PRP group. Conclusions Thorough physical and chemical treatments can reduce the probability of immune rejection of DBMs. The novel composite of DBMs mixed with PRP can serve as a promising bone regeneration material.

Polythiophene (PTh) with highly regular molecular structure is synthesized as nearly amorphous thin films by electrochemical methods in a BFEE/DTBP mixed medium (BFEE = boron fluoride ethyl ether; DTBP = 2,6-di-tert-butypyridine). The doping level and film morphology of PTh are modulated through adjusting the current density applied during the polymerization process. A combined analysis with solid-state NMR, FT-IR, and Raman spectra reveals the molecular structural regularity of the resulted PTh films, which leads to the highest electrical conductivity up to 700 S cm-1 for films obtained under an optimized current density of 1 mA cm-2 . By applying the self-heating 3ω-method, thermal conductivities are measured along the in-plane direction. A highly reduced Lorenz number of 6.49 × 10-9 W Ω K-2 and low lattice thermal conductivity of 0.21 W m-1 K-1 were extracted based on the analyses of the electrical and thermal conductivities according to the Wiedemann-Franz Law; the former is about one-third of the Sommerfeld value. Finally, the maximized ZT value can reach up to 0.10 under room temperature, which shows that the highly conducting polymers with less ordered structure is the practical direction for developing organic thermoelectric materials.

A diabetic foot ulcer (DFUs) is a state of prolonged chronic inflammation, which can result in amputation. Different from normal skin wounds, various commercially available dressings have not sufficiently improved the healing of DFUs. In this study, a novel self-healing hydrogel was prepared by in situ crosslinking of N-carboxyethyl chitosan ( N-chitosan) and adipic acid dihydrazide (ADH) with hyaluronic acid-aldehyde (HA-ALD), to provide a moist and inflammatory relief environment to promote stem cell proliferation or secretion of growth factors, thus accelerating wound healing. The results demonstrated that this injectable and self-healing hydrogel has excellent swelling properties, stability, and mechanical properties. This biocompatible hydrogel stimulated secretion of growth factors from bone marrow mesenchymal stem cells (BM-MSCs) and regulated the inflammatory environment by inhibiting the expression of M1 macrophages and promoting the expression of M2 macrophages, resulting in granulation tissue formation, collagen deposition, nucleated cell proliferation, neovascularization, and enhanced diabetic wound healing. This study showed that N-chitosan/HA-ALD hydrogel could be used as a multifunctional injectable wound dressing to regulate chronic inflammation and provide an optimal environment for BM-MSCs to promote diabetic wound healing.

Nanocrystals of a 2D π-d conjugated copper bis(diselenolene) coordination polymer (Cu-BHS, BHS = benzenehexaselenolate) are synthesized via a simple homogeneous reaction between cupric ions and benzenehexaselenol (H6BHS). Its 2D extended hexagonal lattice is confirmed by powder X-ray diffraction, and further characterized by scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. The electrical conductivity measured on compressed powder sample reaches 110 S cm-1 at 300 K, which is among the highest value ever reported for coordination polymers. Furthermore, the intrinsic metallic characteristics of Cu-BHS are confirmed by ultraviolet photoelectron spectroscopy and band structure calculation.