[Design and Implementation of Quality and Safety Traceability System for Reusable Medical Devices Disinfection Based on RFID Technology].

Focusing on the requirements of visual traceability for reprocessing of reused medical devices under the background of deep integration of intelligent medical treatment, a quality and safety traceability system for disinfection of reused medical devices is developed. The multi-dimensional data of the reprocessing chain of reusable medical devices are acquired in real time by the RFID mobile terminal handset and stored temporarily. The data package is formatted based on LoRa protocol and uploaded to the management and control platform in multi-threaded transmission mode for in-depth analysis and traceability. The corresponding prototype system is developed. The first-line operation and maintenance test results show that the prototype system has strong cooperation, strong operation robustness, and obvious advantages in the identification rate and other layers of sterile equipment package.

Injectable Catalyst-Free Poly(Propylene Fumarate) System Cross-Linked by Strain Promoted Alkyne-Azide Cycloaddition Click Chemistry for Spine Defect Filling.

A new PPF-BCN/hyPCL32-N3 injectable system that can be cross-linked by catalyst-free, strain promoted alkyne-azide cycloaddition (SPAAC) click chemistry was developed for tissue engineering applications. The system consisted of two components: PPF-BCN, poly(propylene fumarate) (PPF) functionalized with (1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN-OH), and hyPCL32-N3, a hyper-branched 32-arm poly(ε-caprolactone) (PCL) dendrimer functionalized with azide as the cross-linker core. Fast SPAAC click reaction allowed the desired gelation of the system without using any toxic initiator or catalyst. Compared to the conventional injectable formulation, e.g., poly(methyl methacrylate) (PMMA), our PPF-BCN/hyPCL32-N3 (abbreviated as PFCL-Click) injectable system showed enhanced biocompatibility and low heat generation during cross-linking. After reaction, the cross-linked PFCL-Click scaffolds supported excellent proliferation and differentiation of preosteoblast cells on the surface. The PFCL-Click system can be successfully injected into vertebral bodies of rabbit spine and can be monitored by X-ray imaging after incorporating zirconium dioxide (ZrO2) powder. With these unique advantages, this injectable system has promising potential for bone defect repair and other tissue engineering and regenerative medicine applications.

Poly(Propylene Fumarate)-Hydroxyapatite Nanocomposite Can Be a Suitable Candidate for Cervical Cages.

A wide range of materials have been used for the development of intervertebral cages. Poly(propylene fumarate) (PPF) has been shown to be an excellent biomaterial with characteristics similar to trabecular bone. Hydroxyapatite (HA) has been shown to enhance biocompatibility and mechanical properties of PPF. The purpose of this study was to characterize the effect of PPF augmented with HA (PPF:HA) and evaluate the feasibility of this material for the development of cervical cages. PPF was synthesized and combined with HA at PPF:HA wt:wt ratios of 100:0, 80:20, 70:30, and 60:40. Molds were fabricated for testing PPF:HA bulk materials in compression, bending, tension, and hardness according to ASTM standards, and also for cage preparation. The cages were fabricated with and without holes and with porosity created by salt leaching. The samples as well as the cages were mechanically tested using a materials testing frame. All elastic moduli as well as the hardness increased significantly by adding HA to PPF (p < 0.0001). The 20 wt % HA increased the moduli significantly compared to pure PPF (p < 0.0001). Compressive stiffness of all cages also increased with the addition of HA. HA increased the failure load of the porous cages significantly (p = 0.0018) compared with nonporous cages. PPF:HA wt:wt ratio of 80:20 proved to be significantly stiffer and stronger than pure PPF. The current results suggest that this polymeric composite can be a suitable candidate material for intervertebral body cages.

[Advantages of foley catheter for nephrostomy tube after minimally invasive percutaneous nephrolithotomy].

OBJECTIVE: To assess the advantages and nursing experience of foley catheter for nephrostomy tube after minimally invasive percutaneous nephrolithotomy (mPCNL).
 Methods: From October 2015 to April 2016, the clinical data of 137 patients, who were diagnosed with upper urinary tract calculi and need to perform mPCNL, were collected and randomized into 2 groups: a foley catheter group (research group, n=69) and a normal nephrostomy tube group (control group, n=68). The patients in research group used foley catheter for nephrostomy tube, while those in the control group used normal nephrostomy tube. Bleeding volume, the days of bleeding, pipes shedding and pain degree were compared, and the experience of the nursing process was summarized.
 Results: The bleeding volume, the days of bleeding in the research group were significantly lower than those in the control group (both P<0.01). The pipes shedding rate in the research group were lower than that in the control group (P<0.05). There was no significant difference in postoperative pain scores between the 2 groups (P>0.05). There was no other complications and discomfortable symptoms in the experimental group.
 Conclusion: The use of foley catheter for nephrostomy tube after mPCNL is safe, and it can decrease the bleeding volume and pipes shedding rate. It doesn't increase the patient's postoperative pain and can reduce the difficulty and risk for postoperative nursing.

[Expression of matrix Gla protein and bone morphogenetic protein 2 in renal papillary tissues in patients with calcium oxalate kidney stones].

OBJECTIVE: To compare expression levels of matrix Gla protein (MGP) and bone morphogenetic protein 2 (BMP-2) in Randall's plaque of renal papillary tissues in patients with calcium oxalate kidney stones and the underlying mechanism for stone formation.
 Methods: A total of 30 samples of Randall's plaque in renal papillary tissues from patients with calcium oxalate kidney stones were collected from the Department of Urology of Xiangya Hospital of Central South University from April, 2015 to December, 2015 and served as an experimental group. Ten samples of renal papillary tissues in patients undergone renal tumor nephrectomy were collected from the same hospital and served as a control group. The expressions of MGP and BMP-2 mRNA and protein were detected by quantitative real-time PCR and Western blot.Meanwhile, immunohistochemical technique was used to observe the expressions of MGP and BMP-2 in different parts of renal papillary tissues in the 2 groups.
 Results: 1) The mRNA expression levels of MGP in the experimental group and the control group were 0.760±0.804 and 1.365±0.348, respectively, with significant difference between them (P<0.05). Them RNA levels of BMP-2 in the experimental group and the control group were 2.500±0.725 and 1.485±0.870, respectively, with significant difference between them (P<0.05). The expression levels of MGP protein in the experimental group and the control group were 0.130±0.424 and 0.202±0.704, respectively, with no significant difference between them (P>0.05). The expression levels of BMP-2 protein in the experimental group and the control group were 0.885±0.220 and 0.682±0.272, respectively, with significant difference between them (P<0.05). The immunohistochemistry showed that the protein expression of MGP in the experimental group was lower than that in the control group, while the protein expression of BMP-2 in the experimental group was higher than that in the control group (both P<0.05).
 Conclusion: The BMP-2 expression is increased while MGP expression is decreased in renal papillary tissues in patients with calcium oxalate kidney stones, and the formation of calcium oxalate kidney stone might be a kind of osteogenetic reaction or ectopic calcification.

Roles of hydroxyapatite allocation and microgroove dimension in promoting preosteoblastic cell functions on photocured polymer nanocomposites through nuclear distribution and alignment.

This study clarifies how hydroxyapatite (HA) allocation and microgroove dimension affect mouse preosteoblastic MC3T3-E1 cell functions on microgrooved substrates of polymer nanocomposites. Using replica molding from micromachined silicon wafer templates, we fabricated photocured poly(ε-caprolactone) triacrylate (PCLTA)/HA nanocomposite substrates with parallel microgrooves (two groove widths of 5 and 15 µm and one groove depth of 5 µm). Four types of microgrooved substrates were made: "homogeneous" ones of PCLTA and PCLTA/HA with uniform distribution and two "heterogeneous" laminated microgrooved substrates with HA only in the PCLTA matrix in the ridges or bottom. These substrates were used to regulate MC3T3-E1 cell attachment, proliferation, alignment, nuclear circularity and distribution, and mineralization. MC3T3-E1 cell attachment and proliferation were much higher on the microgrooved substrates of PCLTA/HA than on those of PCLTA, in particular, on the 5 µm wide microgrooved substrate with PCLTA/HA ridges and PCLTA bottom. The shape and distribution of MC3T3-E1 cytoskeleton and nuclei were altered by the substrate topography and HA allocation. For 5 µm wide heterogeneous microgrooved substrates with HA only in the ridges, MC3T3-E1 cells exhibited better spreading perpendicular to the microgrooves but tended to extend along the microgrooves containing HA in the bottom. The widest cells and the roundest/largest cell nuclei were observed on the heterogeneous substrate with PCLTA/HA ridges, while the narrowest cells with the best elongation were found on the homogeneous PCLTA/HA substrate. The trend in MC3T3-E1 cell mineralization on the substrates was consistent with that in cell/nuclear elongation. Osteocalcin mRNA expression was significantly higher on the PCLTA/HA substrates than on the PCLTA ones and also on the microgrooved substrates of PCLTA/HA than on the flat ones, regardless of the groove width of 5 or 15 µm.

Spinal fusion of biodegradable poly(propylene fumarate) and poly(propylene fumarate-co-caprolactone) copolymers in rabbits.

Background: Autologous bone grafts are currently the standard in orthopedic surgery despite limited donor sources and the prevalence of donor site morbidity. Other alternatives such as allografts are more readily available than autografts but have lower rates of graft incorporation. Methods: Here, we propose a novel graft alternative consisting of an injectable poly(propylene fumarate) (PPF) and poly(propylene fumarate-co-caprolactone) P(PF-co-CL) copolymer with a recombinant human bone morphogenetic protein-2 (rhBMP-2)/vascular epithelial growth factor (VEGF) release system accompanied by hydroxyapatite (HA). The efficacy of scaffold formulations was studied using a standard, bilateral, L-level (L5-L6) posterolateral transverse spinal fusion using New Zealand white rabbits. Rabbits were divided into 4 experimental groups: group I, negative control; group II, autograft (positive control); group III, injectable PPF scaffold with rhBMP-2/VEGF release system and HA; group IV, injectable P(PF-co-CL)scaffold with rhBMP-2/VEGF release system and HA. Spines were harvested at 6 weeks and 12 weeks after surgery, and spinal fusions were assessed using manual palpation, radiographic analysis, micro-computed tomography (µCT) assessment, and histologic analysis. Results: Of the 4 experimental groups, the injectable P(PF-co-CL) scaffold displayed superior initial strength and faster degradation than scaffolds constructed from PPF alone and facilitated the fusion of lateral processes in the rabbit standard posterolateral spinal fusion model. The results obtained from manual palpation, radiology, and µCT showed no difference between the P(PF-co-CL) group and the PPF group. However, histologic sections showed more osteogenesis with the new injectable P(PF-co-CL) scaffold. Conclusion: Injectable P(PF-co-CL) polymers showed promising spine fusion abilities in rabbits after 12 weeks of posterolateral implantation.

Extrusion 3D-printing and characterization of poly(caprolactone fumarate) for bone regeneration applications.

Polycaprolactone fumarate (PCLF) is a cross-linkable PCL derivative extensively considered for tissue engineering applications. Although injection molding has been widely used to develop PCLF scaffolds, platforms developed using such technique lack precise control on architecture, design, and porosity required to ensure adequate cellular and tissue responses. In particular, the scaffolds should provide a suitable surface for cell attachment and proliferation, and facilitate cell-cell communication and nutrient flow. 3D printing technologies have led to new architype for biomaterial development with micro-architecture mimicking native tissue. Here, we developed a method for 3D printing of PCLF structures using the extrusion printing technique. The crosslinking property of PCLF enabled the unique post-processing of 3D printed scaffolds resulting in highly porous and flexible PCLF scaffolds with compressive properties imitating natural features of cancellous bone. Generated scaffolds supported excellent attachment and proliferation of mesenchymal stem cells (MSC). The high porosity of PCLF scaffolds facilitated vascularized membrane formation demonstrable with the stringency of the ex ovo chicken chorioallantoic membrane (CAM) implantation. Furthermore, upon implantation to rat calvarium defects, PCLF scaffolds enabled an exceptional new bone formation with a bone mineral density of newly formed bone mirroring native bone tissue. These studies suggest that the 3D-printed highly porous PCLF scaffolds may serve as a suitable biomaterial platform to significantly expand the utility of the PCLF biomaterial for bone tissue engineering applications.

3D Stem Cell Spheroids with 2D Hetero-Nanostructures for In Vivo Osteogenic and Immunologic Modulated Bone Repair.

3D stem cell spheroids have immense potential for various tissue engineering applications. However, current spheroid fabrication techniques encounter cell viability issues due to limited oxygen access for cells trapped within the core, as well as nonspecific differentiation issues due to the complicated environment following transplantation. In this study, functional 3D spheroids are developed using mesenchymal stem cells with 2D hetero-nanostructures (HNSs) composed of single-stranded DNA (ssDNA) binding carbon nanotubes (sdCNTs) and gelatin-bind black phosphorus nanosheets (gBPNSs). An osteogenic molecule, dexamethasone (DEX), is further loaded to fabricate an sdCNTgBP-DEX HNS. This approach aims to establish a multifunctional cell-inductive 3D spheroid with improved oxygen transportation through hollow nanotubes, stimulated stem cell growth by phosphate ions supplied from BP oxidation, in situ immunoregulation, and osteogenesis induction by DEX molecules after implantation. Initial transplantation of the 3D spheroids in rat calvarial bone defect shows in vivo macrophage shifts to an M2 phenotype, leading to a pro-healing microenvironment for regeneration. Prolonged implantation demonstrates outstanding in vivo neovascularization, osteointegration, and new bone regeneration. Therefore, these engineered 3D spheroids hold great promise for bone repair as they allow for stem cell delivery and provide immunoregulative and osteogenic signals within an all-in-one construct.

Propelling Minimally Invasive Tissue Regeneration With Next-Era Injectable Pre-Formed Scaffolds.

The growing aging population, with its associated chronic diseases, underscores the urgency for effective tissue regeneration strategies. Biomaterials play a pivotal role in the realm of tissue reconstruction and regeneration, with a distinct shift toward minimally invasive (MI) treatments. This transition, fueled by engineered biomaterials, steers away from invasive surgical procedures to embrace approaches offering reduced trauma, accelerated recovery, and cost-effectiveness. In the realm of MI tissue repair and cargo delivery, various techniques are explored. While in situ polymerization is prominent, it is not without its challenges. This narrative review explores diverse biomaterials, fabrication methods, and biofunctionalization for injectable pre-formed scaffolds, focusing on their unique advantages. The injectable pre-formed scaffolds, exhibiting compressibility, controlled injection, and maintained mechanical integrity, emerge as promising alternative solutions to in situ polymerization challenges. The conclusion of this review emphasizes the importance of interdisciplinary design facilitated by synergizing fields of materials science, advanced 3D biomanufacturing, mechanobiological studies, and innovative approaches for effective MI tissue regeneration.

Injectable bioactive poly(propylene fumarate) and polycaprolactone based click chemistry bone cement for spinal fusion in rabbits.

Degenerative spinal pathology is a widespread medical issue, and spine fusion surgeries are frequently performed. In this study, we fabricated an injectable bioactive click chemistry polymer cement for use in spinal fusion and bone regrowth. Taking advantages of the bioorthogonal click reaction, this cement can be crosslinked by itself eliminating the addition of a toxic initiator or catalyst, nor any external energy sources like UV light or heat. Furthermore, nano-hydroxyapatite (nHA) and microspheres carrying recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human vascular endothelial growth factor (rhVEGF) were used to make the cement bioactive for vascular induction and osteointegration. After implantation into a rabbit posterolateral spinal fusion (PLF) model, the cement showed excellent induction of new bone formation and bridging bone, achieving results comparable to autograft control. This is largely due to the osteogenic properties of nano-hydroxyapatite (nHA) and the released rhBMP-2 and rhVEGF growth factors. Since the availability of autograft sources is limited in clinical settings, this injectable bioactive click chemistry cement may be a promising alternative for spine fusion applications in addressing various spinal conditions.

Bioactive Moldable Click Chemistry Polymer Cement with Nano-Hydroxyapatite and Growth Factor-Enhanced Posterolateral Spinal Fusion in a Rabbit Model.

Spinal injuries or diseases necessitate effective fusion solutions, and common clinical approaches involve autografts, allografts, and various bone matrix products, each with limitations. To address these challenges, we developed an innovative moldable click chemistry polymer cement that can be shaped by hand and self-cross-linked in situ for spinal fusion. This self-cross-linking cement, enabled by the bioorthogonal click reaction, excludes the need for toxic initiators or external energy sources. The bioactivity of the cement was promoted by incorporating nanohydroxyapatite and microspheres loaded with recombinant human bone morphogenetic protein-2 and vascular endothelial growth factor, fostering vascular induction and osteointegration. The release kinetics of growth factors, mechanical properties of the cement, and the ability of the scaffold to support in vitro cell proliferation and differentiation were evaluated. In a rabbit posterolateral spinal fusion model, the moldable cement exhibited remarkable induction of bone regeneration and effective bridging of spine vertebral bodies. This bioactive moldable click polymer cement therefore presents a promising biomaterial for spinal fusion augmentation, offering advantages in safety, ease of application, and enhanced bone regrowth.

Bioorthogonal "Click Chemistry" Bone Cement with Bioinspired Natural Mimicking Microstructures for Bone Repair.

Current bone cement systems often demand free radical or metal-related initiators and/or catalysts for the crosslinking process, which may cause serious toxicity to the human body. In addition, the resultant dense scaffolds may have a prolonged degradation time and are difficult for cells to infiltrate and form new tissue. In this study, we developed a porous "click" organic-inorganic nanohybrid (PO-click-ON) cement that crosslinks via metal-free biorthogonal click chemistry and forms porous structures mimicking the native bone tissue via particulate leaching. Strain-promoted click reaction enables fast and efficient crosslinking of polymer chains with the exclusion of any toxic initiator or catalyst. The resulting PO-click-ON implants supported exceptional in vitro stem cell adhesion and osteogenic differentiation with a large portion of stem cells infiltrated deep into the scaffolds. In vivo study using a rat cranial defect model demonstrated that the PO-click-ON system achieved outstanding cell adsorption, neovascularization, and bone formation. The porous click cement developed in this study serves as a promising platform with multifunctionality for bone and other tissue engineering applications.

Visible light-induced 3D bioprinted injectable scaffold for minimally invasive tissue regeneration.

Pre-formed hydrogel scaffolds have emerged as favorable vehicles for tissue regeneration, promoting minimally invasive treatment of native tissue. However, due to the high degree of swelling and inherently poor mechanical properties, development of complex structural hydrogel scaffolds at different dimensional scales has been a continuous challenge. Herein, we take a novel approach at the intersections of engineering design and bio-ink chemistry to develop injectable pre-formed structural hydrogel scaffolds fabricated via visible light (VL) induced digital light processing (DLP). In this study, we first determined the minimum concentration of poly(ethylene glycol) diacrylate (PEGDA) to be added to the gelatin methacrylate (GelMA) bio-ink in order to achieve scalable and high printing-fidelity with desired cell adhesion, viability, spreading, and osteogenic differentiation characteristics. Despite the advantages of hybrid GelMA-PEGDA bio-ink in improving scalability and printing-fidelity, compressibility, shape-recovery, and injectability of the 3D bioprinted scaffolds were compromised. To restore these needed characteristics for minimally invasive tissue regeneration applications, we performed topological optimization to design highly compressible and injectable pre-formed (i.e., 3D bioprinted) microarchitectural scaffolds. The designed injectable pre-formed microarchitectural scaffolds showed a great capacity to retain the viability of the encapsulated cells (>72 % after 10 cycles of injection). Lastly, ex ovo chicken chorioallantoic membrane (CAM) studies revealed that the optimized injectable pre-formed hybrid hydrogel scaffold is biocompatible and supports angiogenic growth.

3D-printed scaffolds with 2D hetero-nanostructures and immunomodulatory cytokines provide pro-healing microenvironment for enhanced bone regeneration.

Three-dimensional (3D) printing technology is driving forward the progresses of various engineering fields, including tissue engineering. However, the pristine 3D-printed scaffolds usually lack robust functions in stimulating desired activity for varied regeneration applications. In this study, we combined the two-dimensional (2D) hetero-nanostructures and immuno-regulative interleukin-4 (IL-4) cytokines for the functionalization of 3D-printed scaffolds to achieve a pro-healing immuno-microenvironment for optimized bone injury repair. The 2D hetero-nanostructure consists of graphene oxide (GO) layers, for improved cell adhesion, and black phosphorous (BP) nanosheets, for the continuous release of phosphate ions to stimulate cell growth and osteogenesis. In addition, the 2D hetero-nanolayers facilitated the adsorption of large content of immuno-regulative IL-4 cytokines, which modulated the polarization of macrophages into M2 phenotype. After in vivo implantation in rat, the immuno-functioned 3D-scaffolds achieved in vivo osteo-immunomodulation by building a pro-healing immunological microenvironment for better angiogenesis and osteogenesis in the defect area and thus facilitated bone regeneration. These results demonstrated that the immuno-functionalization of 3D-scaffolds with 2D hetero-nanostructures with secondary loading of immuno-regulative cytokines is an encouraging strategy for improving bone regeneration.

Anti-BCMA surface engineered biomimetic photothermal nanomissile enhances multiple myeloma cell apoptosis and overcomes the disturbance of NF-κB signaling in vivo.

Conventional chemotherapy for multiple myeloma (MM) faces the challenges of a low complete remission rate and transformation to recurrence/refractory. The current MM first-line clinical drug Bortezomib (BTZ) faces the problem of enhanced tolerance and nonnegligible side effects. B cell maturation antigen (BCMA), for its important engagement in tumor signaling pathways and novel therapy technologies such as Chimeric antigen receptor T-Cell immunotherapy (CAR-T) and Antibody Drug Conjugate (ADC), has been identified as an ideal target and attracted attention in anti-MM therapy. Emerging nanotechnology provided feasible methods for drug delivery and new therapeutic strategies such as photothermal therapy (PTT). Herein, we developed a BCMA-Targeting biomimetic photothermal nanomissile BTZ@BPQDs@EM @anti-BCMA (BBE@anti-BCMA) by integration of BTZ, black phosphorus quantum dots (BPQDs), Erythrocyte membrane (EM) and BCMA antibody (anti-BCMA). We hypothesized that this engineered nanomissile could attack tumor cells in triple ways and achieve effective treatment of MM. Consequently, the intrinsic biomimetic nature of EM and the active targeting property of anti-BCMA enhanced the accumulation of therapeutic agents in the tumor site. Besides, owing to the decrease in BCMA abundance, the potential apoptosis-inducing ability was revealed. With the support of BPQDs' photothermal effect, Cleaved-Caspase-3 and Bax signal increased significantly, and the expression of Bcl-2 was inhibited. Furthermore, the synergistic photothermal/chemo therapy can effectively inhibit tumor growth and reverse the disorder of NF-κB in vivo. Importantly, this biomimetic nanodrug delivery system and antibody induced synergistic therapeutic strategy efficiently killed MM cells with ignorable systemic toxicity, which is a promising method for the future anticancer treatment of hematological malignancies in clinics.

Size-dependent osteogenesis of black phosphorus in nanocomposite hydrogel scaffolds.

A promising new strategy emerged in bone tissue engineering is to incorporate black phosphorus (BP) into polymer scaffolds, fabricating nanocomposite hydrogel platforms with biocompatibility, degradation controllability, and osteogenic capacity. BP quantum dot is a new concept and stands out recently among the BP family due to its tiny structure and a series of excellent characteristics. In this study, BP was processed into nanosheets of three different sizes via different exfoliation strategies and then incorporated into cross-linkable oligo[poly(ethylene glycol) fumarate] (OPF) to produce nanocomposite hydrogels for bone regeneration. The three different BP nanosheets were designated as BP-L, BP-M, and BP-S, with a corresponding diameter of 242.3 ± 90.0, 107.1 ± 47.9, and 18.8 ± 4.6 nm. The degradation kinetics and osteogenic capacity of MC3T3 pre-osteoblasts in vitro were both dependent on the BP size. BP exhibited a controllable degradation rate, which increased with the decrease of the size of the nanosheets, coupled with the release of phosphate in vitro. The osteogenic capacity of the hydrogels was promoted with the addition of all BP nanosheets, compared with OPF hydrogel alone. The smallest BP quantum dots was shown to be optimal in enhancing MC3T3 cell behaviors, including spreading, distribution, proliferation, and differentiation on the OPF hydrogels. These results reinforced that the supplementation of BP quantum dots into OPF nanocomposite hydrogel scaffolds could potentially find application in the restoration of bone defects.

Injectable pH-responsive adhesive hydrogels for bone tissue engineering inspired by the underwater attachment strategy of marine mussels.

A major challenge in tissue engineering is the development of alternatives to traditional bone autografts and allografts that can regenerate critical-sized bone defects. Here we present the design of injectable pH-responsive double-crosslinked adhesive hydrogels inspired by the molecular mechanism and environmental post-processing of marine mussel adhesive. Nine adhesive hydrogel formulations were developed through the conjugation of crosslinkable catechol functional groups (DOPA) and the synthetic oligomer oligo[poly(ethylene glycol) fumarate] (OPF), varying the DOPA content (w/w%) and molecular weight (MW) of the OPF backbone to produce formulations with a range of swelling ratios, porosities, and crosslink densities. DOPA incorporation altered the surface chemistry, mechanical properties, and surface topography of hydrogels, resulting in an increase in material stiffness, slower degradation, and enhanced pre-osteoblast cell attachment and proliferation. When injected within simulated bone defects, DOPA-mediated interfacial adhesive interactions also prevented the displacement of scaffolds, an effect that was maintained even after swelling within physiological conditions. Taken together, OPF-DOPA hydrogels represent a promising new material to enhanced tissue integration and the prevention of the post-implantation migration of scaffolds that can occur due to biomechanical loading in vivo.

Two-dimensional nanomaterials-added dynamism in 3D printing and bioprinting of biomedical platforms: Unique opportunities and challenges.

The nanomaterials research spectrum has seen the continuous emergence of two-dimensional (2D) materials over the years. These highly anisotropic and ultrathin materials have found special attention in developing biomedical platforms for therapeutic applications, biosensing, drug delivery, and regenerative medicine. Three-dimensional (3D) printing and bioprinting technologies have emerged as promising tools in medical applications. The convergence of 2D nanomaterials with 3D printing has extended the application dynamics of available biomaterials to 3D printable inks and bioinks. Furthermore, the unique properties of 2D nanomaterials have imparted multifunctionalities to 3D printed constructs applicable to several biomedical applications. 2D nanomaterials such as graphene and its derivatives have long been the interest of researchers working in this area. Beyond graphene, a range of emerging 2D nanomaterials, such as layered silicates, black phosphorus, transition metal dichalcogenides, transition metal oxides, hexagonal boron nitride, and MXenes, are being explored for the multitude of biomedical applications. Better understandings on both the local and systemic toxicity of these materials have also emerged over the years. This review focuses on state-of-art 3D fabrication and biofabrication of biomedical platforms facilitated by 2D nanomaterials, with the comprehensive summary of studies focusing on the toxicity of these materials. We highlight the dynamism added by 2D nanomaterials in the printing process and the functionality of printed constructs.

Scaffold-Free Spheroids with Two-Dimensional Heteronano-Layers (2DHNL) Enabling Stem Cell and Osteogenic Factor Codelivery for Bone Repair.

Scaffold-free spheroids offer great potential as a direct supply of cells for bottom-up bone tissue engineering. However, the building of functional spheroids with both cells and bioactive signals remains challenging. Here, we engineered functional spheroids with mesenchymal stem cells (MSCs) and two-dimensional heteronano-layers (2DHNL) that consisted of black phosphorus (BP) and graphene oxide (GO) to create a 3D cell-instructive microenvironment for large defect bone repair. The effects of the engineered 2D materials on the proliferation, osteogenic differentiation of stem cells was evaluated in an in vitro 3D spheroidal microenvironment. Excellent in vivo support of osteogenesis of MSCs, neovascularization, and bone regeneration was achieved after transplanting these engineered spheroids into critical-sized rat calvarial defects. Further loading of osteogenic factor dexamethasone (DEX) on the 2DHNL showed outstanding in vivo osteogenic induction and bone regrowth without prior in vitro culture in osteogenic medium. The shortened overall culture time would be advantageous for clinical translation. These functional spheroids impregnated with engineered 2DHNL enabling stem cell and osteogenic factor codelivery could be promising functional building blocks to provide cells and differential clues in an all-in-one system to create large tissues for time-effective in vivo bone repair.