Bone morphogenetic protein-2 and pulsed electrical stimulation synergistically promoted osteogenic differentiation on MC-3T3-E1 cells.

Electrical stimulation (ES) plays an important role in regulating cell osteoblast differentiation. As a noninvasive rehabilitation therapy method, Es has a unique role in postoperative recovery. Bone morphogenetic protein-2 (BMP-2) is the most commonly used bioactive molecule in in situ tissue engineering scaffolds, and it plays an important regulatory role in the whole process of bone injury repair. In this study, the osteogenic regulation of MC-3T3-E1 cells was studied by combining pulsed electrical stimulation (PES) and different concentrations of BMP-2. The results showed that PES and BMP-2 could synergically promote the proliferation of MC-3T3-E1 cells. The qPCR results of osteoblast-related genes showed that PES was synergistic with BMP-2 to promote osteoblast differentiation mainly through the regulation of the Smad/BMP and insulin like growth factor 1 (IGF1) signaling pathways. The expression level of alkaline phosphatase (ALP) and alizarin red staining further demonstrated the synergistic effect of PES and BMP-2 on promoting osteogenic differentiation and mineralization of cells. PES and BMP-2 could also synergically promote cell proliferation, expression of collagen I (COL-I) and ALP, and cell mineralization on the 3D-printed polylactic acid scaffold. These results suggest that the use of PES can enhance the osteogenic effect of in situ bone repair scaffolds containing BMP-2, reduce the dose of BMP-2 alone, and reduce the possible side effects of high-dose BMP-2 in vivo.

Surface Biofunctionalization of Gadolinium Phosphate Nanobunches for Boosting Osteogenesis/Chondrogenesis Differentiation.

In order to achieve smart biomedical micro/nanomaterials, promote interaction with biomolecules, improve osteogenic/chondrogenic differentiation, exhibit better dispersion in bone implants and ultimately maximize functionality, we innovatively and successfully designed and synthesized polymer PBLG-modified GdPO4·H2O nanobunches by hydroxylation, silylation and glutamylation processes. The effects of different feeding ratios on the surface coating of GdPO4·H2O with Si-OH, the grafting γ-aminopropyltriethoxysilane (APS) and the in situ ring-opening polymerization reaction of poly(g-benzyl-L-glutamate) (PBLG) were investigated, and the physical and chemical properties were characterized in detail. When GdPO4·H2O@SiO2-APS:NCA = 4:1, the PBLG-g-GdPO4·H2O grafting rate was 5.93%, with good stability and dispersion in degradable polymeric materials. However, the MRI imaging signal was sequentially weakened as the modification process proceeded. Despite this, the biological effects had surprising findings. All the modifiers at appropriate concentrations were biocompatible and biologically active and the biomacromolecules of COL I and COL II in particular were expressed at least 3 times higher in GdPO4·H2O@SiO2 compared to the PLGA. This indicates that the appropriate surface modification and functionalization of gadolinium-containing micro/nanomaterials can promote interaction with cells and encourage bone regeneration by regulating biomacromolecules and can be used in the field of biomedical materials.

Binding efficiency of recombinant collagen-binding basic fibroblast growth factors (CBD-bFGFs) and their promotion for NIH-3T3 cell proliferation.

The recombinant basic fibroblast growth factor (bFGF) containing collagen-binding domain (CBD) has been found to be a potential therapeutic factor in tissue regeneration. However, its binding efficiency and quantification remain uncertain. In this research, massive recombinant bFGFs with good bioactivity for enhancing the proliferation of NIH-3T3 cells were achieved. An ELISA-based quantitative method was set up to investigate the binding efficiency of CBD-bFGFs on collagen films. It indicated that the CBDs significantly increased the collagen-binding ability of bFGF (P < .05), with the optimum binding condition first determined to be in the pH range of 7.5-9.5 (P < .05). Then, the relevant equations to calculate the binding density of bFGF, C-bFGF, and V-bFGF were acquired. Analysis confirmed that the bioactivity of immobilized bFGFs was well correlated with the density of growth factor on collagen films. Based on this research, the density of growth factor is a logical and applicable dosage unit for quantification of binding efficiency of growth factors, rather than traditional concentration of soluble growth factors in tissue engineering applications.

Enhanced in Vitro Mineralization and in Vivo Osteogenesis of Composite Scaffolds through Controlled Surface Grafting of L-Lactic Acid Oligomer on Nanohydroxyapatite.

Nanocomposite of hydroxyapatite (HA) surface grafted with L-lactic acid oligomer (LAc oligomer) (op-HA) showed improved interface compatibility, mechanical property, and biocompatibility in our previous study. In this paper, composite scaffolds of op-HA with controlled grafting different amounts of LAc oligomer (1.1, 5.2, and 9.1 wt %) were fabricated and implanted to repair rabbit radius defects. The dispersion of op-HA nanoparticles was more uniform than n-HA in chloroform and nanocomposites scaffold. Calcium and phosphorus exposure, in vitro biomineralization ability, and cell proliferation were much higher in the op-HA1.1 wt %/PLGA scaffolds than the other groups. The osteodifferentiation and bone fusion in animal tests were significantly enhanced for op-HA5.2 wt %/PLGA scaffolds. The results indicated that the grafted LAc oligomer of 5.2 or 9.1 wt %, which formed a barrier layer on the HA surface, prevented the exposure of nucleation sites. The shielded nucleation sites of op-HA particles (5.2 wt %) might be easily exposed as the grafted LAc oligomer was decomposed easily by enzyme systems in vivo. Findings from this study have revealed that grafting 1.1 wt % amount of LAc oligomer on hydroxyapatite could improve in vitro mineralization, and 5.2 wt % could promote in vivo osteogenesis capacity of composite scaffolds.

A Bioorthogonal Approach for the Preparation of a Titanium-Binding Insulin-like Growth-Factor-1 Derivative by Using Tyrosinase.

The generation of metal surfaces with biological properties, such as cell-growth-enhancing and differentiation-inducing abilities, could be potentially exciting for the development of functional materials for use in humans, including artificial dental implants and joint replacements. However, currently the immobilization of proteins on the surfaces of the metals are limited. In this study, we have used a mussel-inspired bioorthogonal approach to design a 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth-factor-1 using a combination of recombinant DNA technology and tyrosinase treatment for the surface modification of titanium. The modified growth factor prepared in this study exhibited strong binding affinity to titanium, and significantly enhanced the growth of NIH3T3 cells on the surface of titanium.

In vitro study of electroactive tetraaniline-containing thermosensitive hydrogels for cardiac tissue engineering.

Injectable hydrogels made of degradable biomaterials can function as both physical support and cell scaffold in preventing infarct expansion and promoting cardiac repair in myocardial infarction therapy. Here, we report in situ hydrogels consisting of thermosensitive PolyNIPAM-based copolymers and electroactive tetraaniline (TA). Studies showed that the addition of 2-methylene-1,3-dioxepane (MDO) provided the PolyNIPAM-based gel with biodegradability, and the introduction of tetraaniline endowed these copolymers with desirable electrical properties and antioxidant activities. The encapsulated H9c2 cells (rat cardiac myoblast) remained highly viable in the gel matrices. In vivo gel formation and histological analyses were performed in rats by subcutaneous injection and excellent biocompatibility was observed. Furthermore, the proliferation and intracellular calcium transients of H9c2 cells were also studied with (and without) electrical stimuli. Both in vitro and in vivo results demonstrated that electroactive hydrogel may be used as a promising injectable biomaterial for cardiac tissue engineering.

In vitro studies on regulation of osteogenic activities by electrical stimulus on biodegradable electroactive polyelectrolyte multilayers.

In this study, a novel electroactive tetreaniline-containing degradable polyelectrolyte multilayer film (PEM) coating [(poly(l-glutamic acid)-graft-tetreaniline/poly(l-lysine)-graft-tetreaniline)n, (PGA-g-TA/PLL-g-TA)n] was designed and fabricated by layer-by-layer (LbL) assembly method. Compared with the nongrafted PEMs, the tetreaniline-grafted PEMs showed higher roughness and stiffness in micro/nanoscale structures. The special surface characteristics and the typical electroconductive properties were more beneficial for adhesion, proliferation, and differentiation of preosteoblast MC3T3-E1 cells. Moreover, the enhanced effects were observed on the modulation of MC3T3-E1 cells that differentiated into maturing osteoblasts, when the electroactive PEMs were coupled with electrical stimulus (ES), especially in the early phase of the osteoblast differentiation. The alkaline phosphatase (ALP) activity, calcium deposition, immunofluorescence staining, and RT-qPCR were evaluated on the differentiation of preosteoblast. These data indicate that the comprehensive effects through coupling electroactive scaffolds with electrical stimulus are better to develop bioelectric strategies to control cell functions for bone regeneration.

Glucose microenvironment sensitive degradation of arginine modified calcium sulfate reinforced poly(lactide-co-glycolide) composite scaffolds.

Poly(lactide-co-glycolide) (PLGA) and calcium sulfate composites are promising biodegradable biomaterials but are still challenging to use in people with high levels of blood glucose or diabetes. To date, the influence of glucose on their degradation has not yet been elucidated and thus calls for more research attention. Herein, a novel calcium sulfate whisker with L-arginine was used to effectively tune its crystal morphology and was employed as a reinforced phase to construct the PLGA-based composite scaffolds (ArgCSH/PLGA) with a sleeve porous structure. ArgCSH/PLGA showed excellent elastic modulus and strength in the compression and bending models. Moreover, an in vitro immersion test showed that ArgCSH/PLGA possessed degradation and redeposition behaviors sensitive to glucose concentration, and the adsorbed Arg played a crucial role in the degradation process. The subsequent cell functional evaluation showed that ArgCSH could effectively protect cells from damage caused by AGEs and promote osteogenic differentiation. The corresponding degradation products of ArgCSH/PLGA displayed the ability to regulate osteoblast bone differentiation and accelerate matrix mineralization. These findings provide new insights into the interaction between biomaterials and the physiological environment, which may be useful in expanding the targeted choice of efficient bone graft biodegradable materials for diabetic osteoporosis.

Corrigendum to "Dual aldehyde cross-linked hyaluronic acid hydrogels loaded with PRP and NGF biofunctionalized PEEK interfaces to enhance osteogenesis and vascularization" [Mater. Today Bio 24 (2024) 100928].

[This corrects the article DOI: 10.1016/j.mtbio.2023.100928.].

Dual aldehyde cross-linked hyaluronic acid hydrogels loaded with PRP and NGF biofunctionalized PEEK interfaces to enhance osteogenesis and vascularization.

Polyetheretherketone (PEEK) material has become a potential bone replacement material due to its elastic modulus, which is close to that of human bone, and stable chemical properties. However, its biological inertness has hindered its clinical application. To improve the biological inertia of PEEK material, a hyaluronic acid (HA) hydrogel coating loaded with platelet-rich plasma (PRP) and nerve growth factor (NGF) was constructed on the surface of PEEK material in this study. After the hybrid hydrogel coating was constructed, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), degradation tests, and enzyme-linked immunosorbent assays (ELISAs) were used to evaluate its characteristics and biological properties. The osteogenic and angiogenic potentials were also investigated in vitro and in vivo. Our results showed that the HA hydrogel loaded with RPP and NGF on the PEEK surface degraded slowly and could sustainably release various growth factors, including NGF. The results of in vitro tests showed that the hybrid hydrogel on the surface of PEEK effectively promoted osteogenesis and angiogenesis. The in vivo experiment also confirmed that the PEEK surface hydrogel could promote osseointegration of the implant and the integration of new bone and neovascularization. Our results suggest that the cross-linked hyaluronic acid hydrogel loaded with PRP and NGF can significantly improve the biological inertia of PEEK material, endowing PEEK material with good osteogenic and angiogenic ability.

PLA-PEG-PLA and its electroactive tetraaniline copolymer as multi-interactive injectable hydrogels for tissue engineering.

Injectable hydrogels have served as biomimic scaffolds that provide a three-dimensional (3D) structure for tissue engineering or carriers for cell encapsulation in the biomedical field. In this study, the injectable electroactive hydrogels (IEHs) were prepared by introducing electrical properties into the injectable materials. Carboxyl-capped tetraaniline (CTA) as functional group was coupled with enantiomeric polylactide-poly(ethylene glycol)-polylactide (PLA-PEG-PLA), and the electroactive hydrogels were obtained by mixing the enantiomeric copolymers of CTA-PLLA-PEG-PLLA-CTA and CTA-PDLA-PEG-PDLA-CTA aqueous solutions. ultraviolet-visible spectroscopy (UV-vis) and cyclic voltammetry (CV) of the complex solution showed good electroactive properties. The gelation mechanism and intermolecular multi-interactions such as stereocomplextion, hydrogen bonding, and π-π stacking were studied by Fourier transform infrared spectroscopy (FT-IR), UV-vis, and wide-angle X-ray diffraction (WAXD). Gelation properties of the complexes were also studied by rheometer. The encapsulated cells remained highly viable in the gel matrices, suggesting that the hydrogels have excellent cytocompatibility. After subcutaneous injection, the gels were formed in situ in the subcutaneous layer, and hematoxylin-eosin (H&E) staining suggested acceptable biocompatibility of our materials in vivo. Moreover, these injectable materials, when treated with pulsed electrical stimuli, were shown to be functionally active and to accelerate the proliferation of encapsulated fibroblasts, cardiomyocytes, and osteoblasts. Hence, the IEHs possessing these excellent properties would be potentially used as in vivo materials for tissue engineering scaffold.

Influence of foot excitation and shin posture on the vibration behavior of the entire spine inside a seated human body.

Due to ethical issues and simplification of traditional biomechanical models, experimental methods and traditional computer methods were difficult to quantify the effects of foot excitation and shin posture on vibration behavior of the entire spine inside a seated human body under vertical whole-body vibration. This study developed and verified different three-dimensional (3D) finite element (FE) models of seated human body with detailed anatomical structure under the biomechanical characteristics to predict vibration behavior of the entire spine inside a seated human body with different foot excitation (with and without vibration) and shin posture (vertical and tilt posture). Random response analysis was performed to study the transmissibility of the entire spine to seat under vertical white noise excitation between 0 and 20 Hz at 0.5 m/s2 r.m.s. The results showed that although the foot excitation could reduce the fore-aft transmissibility in the cervical spine (23% reduction), it could significantly increase that in the lumbar spine (52% increase), which resulted in complex alternating stresses at lumbar spine and made the lumbar spine more vulnerable to injury in long-term vibration environment. Moreover, the shin tilt posture made the maximum fore-aft transmissibility in the lumbar spine move to the upper lumbar spine. The study provided new insights into the influence of foot excitation and shin posture on the vibration behavior of the entire spine inside a seated human body. Foot excitation exposed the lumbar spine to complex alternating stresses and made it more vulnerable to injury in long-term whole body vibration.

PLGA/BGP/Nef porous composite restrains osteoclasts by inhibiting the NF-κB pathway, enhances IGF-1-mediated osteogenic differentiation and promotes bone regeneration.

BACKGROUND: Novel bone substitutes are urgently needed in experimental research and clinical orthopaedic applications. There are many traditional Chinese medicines that have effects on bone repair. However, application of natural medicines in traditional Chinese medicine to bone tissue engineering and its mechanism were rarely reported. RESULTS: In this study, the osteogenic ability of bioactive glass particles (BGPs) and the osteogenic and osteoclastic ability of neferine (Nef) were fused into PLGA-based bone tissue engineering materials for bone regeneration. BGPs were prepared by spray drying and calcination. Particles and Nef were then mixed with PLGA solution to prepare porous composites by the phase conversion method. Here we showed that Nef inhibited proliferation and enhanced ALP activity of MC3T3-E1 cells in a dose- and time-dependent manner. And the composites containing Nef could also inhibit RANKL-induced osteoclast formation (p < 0.05). Mechanistically, the PLGA/BGP/Nef composite downregulated the expression of NFATC1 by inhibiting the NF-κB pathway to restrain osteoclasts. In the other hands, PLGA/BGP/Nef composite was first demonstrated to effectively activate the IGF-1R/PI3K/AKT/mTOR pathway to enhance IGF-1-mediated osteogenic differentiation. The results of animal experiments show that the material can effectively promote the formation and maturation of new bone in the skull defect site. CONCLUSIONS: The PLGA/BGP/Nef porous composite can restrain osteoclasts by inhibiting the NF-κB pathway, enhance IGF-1-mediated osteogenic differentiation and promotes bone regeneration, and has the potential for clinical application.

Magnetic nanocomposites for magneto-promoted osteogenesis: from simulation auxiliary design to experimental validation.

Magnetically actuated mechanical stimulation, as a novel form of intelligent responsive force stimulation, has a great potential for remote spatiotemporal regulation of a variety of life processes. Hence, the optimal design of magnetic nanomaterials for generating magneto-mechanical stimuli becomes an important driving force in the development of magneto-controlled biotherapy. This study aims to clarify the general rule that the surface modification amount of magnetic nanoparticles (NPs) affects the biological behavior (e.g., cell adhesion, proliferation and differentiation) of pre-osteoblast cells. First of all, course-grained molecular dynamics simulations predict that 23.3% graft modification of the NPs can maximize the heterogeneity of the dynamics of the polymer matrix, which may generate enhanced mechanical stimuli. Then, experimentally, iron oxide (IO) NPs grafted with different amounts of poly(γ-benzyl-L-glutamate) (PBLG) were prepared to obtain homogeneous magnetic nanocomposites with improved mechanical properties. Further in vitro cell experiments demonstrate that the grafting amounts of 21.46% and 32.34% of PBLG on IO NPs are the most beneficial for the adhesion and osteogenic differentiation of cells. Simultaneously, the maximized upregulation of the Piezo1 gene indicates that the cells receive the strongest magneto-mechanical stimuli. The consistent conclusion of the experiments and simulations indicates that 20-30% PBLG grafted on the IO surface could maximize the ability of magnetic stimuli to regulate the biological behavior of the cells, which validates the feasibility of simulation auxiliary material design and is of great importance for promoting the application of magneto-controlled biotherapy in bioengineering and biomedicine.

Conductive Polyaniline Particles Regulating In Vitro Hydrolytic Degradation and Erosion of Hydroxyapatite/Poly(lactide-co-glycolide) Porous Scaffolds for Bone Tissue Engineering.

In addition to biocompatibility and bioactivity, scaffolds with superior bone tissue regenerative capacity should possess excellent functionality (e.g., electroactivity and conductivity) and biodegradability matching with the rate of bone reconstruction. However, current conductive scaffolds display a reduced biodegradability rate and weakened biocompatibility. In this study, injectable conductive porous scaffolds were fabricated, incorporating camphor sulfonic acid-doped polyaniline (PANI) into hydroxyapatite/poly(lactide-co-glycolide) (HA/PLGA) scaffolds, using solvent-casting/particulate-leaching methodology. These scaffolds demonstrated excellent electroactivity, conductivity, hydrophilicity, thermodynamic properties, antibacterial properties, and biocompatibility. Their degradation behavior was explored by regulating the PANI content. The results demonstrated that adding an appropriate content of PANI would increase the pore size, porosity, and water absorption of the conductive scaffold and promote the formation of filamentous fiber byproducts with acidic hydrolysates, which accelerated the degradation rate of the scaffold. Owing to π-π stacking and hydrogen bonding, the conductive scaffold with 10 wt % PANI efficiently retarded the decrease in the thermal and mechanical properties of the scaffolds during a 16 week degradation. Thus, better regulation of degradation behavior and correlation would allow conductive porous scaffolds, such as bone implants, to achieve better bone ingrowth and restoration.

PRP coating on different modified surfaces promoting the osteointegration of polyetheretherketone implant.

Introduction: Polyetheretherketone (PEEK) material implants have been applied more and more clinically recently. In order to increase the osteogenic activity of PEEK material, the microstructure change of the material surface and the construction of functional microcoatings have become a hot research topic. This study investigated the ability of PEEK surfaces modified by different methods to carry Platelet-rich plasma (PRP) and the osteogenic ability of different PEEK microstructures after carrying PRP in vivo/in vitro. Methods: In this study, PEEK surfaces were modified by sulfuric acid, gaseous sulfur trioxide and sandpaper. Next, PRP from SD rats was prepared and incubated on PEEK material with different surface microstructures. Lactate dehydrogenase test, scanning electron microscope and Elisa assay was used to evaluate adhesion efficiency of PRP. Then in vitro tests such as CCK-8, ALP staining, ARS staining and RT-qPCR et al were used to further evaluate osteogenesis ability of the PRP coating on PEEK surface. Finally, The tibia defects of SD rats were established, and the new bone was evaluated by Micro-CT, HE staining, and immunofluorescence staining. Results: The sandpaper-polished PEEK with the strongest PRP carrying capacity showed the best osteogenesis. Our study found that the modified PEEK surface with PRP coating has excellent osteogenic ability and provided the basis for the interface selection of PRP for the further application of PEEK materials. Discussion: Among the three PEEK modified surfaces, due to the most PRP carrying and the strongest osteogenic ability in vitro/vivo, the frosted surface was considered to be the most suitable surface for the preparation of PRP coating.

Dual growth factor-modified microspheres nesting human-derived umbilical cord mesenchymal stem cells for bone regeneration.

BACKGROUND: Modular tissue engineering (MTE) is a novel "bottom-up" approach that aims to mimic complex tissue microstructural features. The constructed micromodules are assembled into engineered biological tissues with repetitive functional microunits and form cellular networks. This is emerging as a promising strategy for reconstruction of biological tissue. RESULTS: Herein, we constructed a micromodule for MTE and developed engineered osteon-like microunits by inoculating human-derived umbilical cord mesenchymal stem cells (HUMSCs) onto nHA/PLGA microspheres with surface modification of dual growth factors (BMP2/bFGF). By evaluating the results of proliferation and osteogenic differentiation ability of HUMSCs in vitro, the optimal ratio of the dual growth factor (BMP2/bFGF) combination was derived as 5:5. In vivo assessments showed the great importance of HUMSCs for osteogneic differentiation. Ultimately, direct promotion of early osteo-differentiation manifested as upregulation of Runx-2 gene expression. The vascularization capability was evaluated by tube formation assays, demonstrating the importance of HUMSCs in the microunits for angiogenesis. CONCLUSIONS: The modification of growth factors and HUMSCs showed ideal biocompatibility and osteogenesis combined with nHA/PLGA scaffolds. The micromodules constructed in the current study provide an efficient stem cell therapy strategy for bone defect repair.

Silicon and gadolinium co-doped hydroxyapatite/PLGA scaffolds with osteoinductive and MRI dual functions.

Introduction: An ideal bone repair scaffold should have dual functions of osteoinductive ability and in vivo imaging. In this study, the simultaneous substitution of silicon (Si) and gadolinium (Gd) in hydroxyapatite (HA) as potential multifunctional bone graft materials has been successfully developed. Methods: A series of HA nanoparticles (HA NPs) doped with different proportions of Si and Gd were prepared. The chemical structure and phase composition of the materials were analyzed using Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). The microstructure, magnetic properties, surface potential, and cytotoxicity of the materials were also analyzed. The magnetic resonance imaging (MRI) effect of Gd&Si-HA/poly(lactic-co-glycolic acid) (Gd&Si-HA/PLGA) composite materials was evaluated. Osteogenic-related gene expression, alkaline phosphatase (ALP) level, and mineralization capacity of MC3T3-E1 cultured on Gd&Si-HA/PLGA composite materials were also detected. Results and Discussion: The 1.5Gd&Si-HA@PLGA group showed good ability to promote osteogenic differentiation of cells. The MRI effect of the 1.5Gd&Si-HA@PLGA scaffold was observable. This HA material containing Si and Gd co-doping has a broad application prospect in the field of bone tissue engineering owing to its ability to enhance osteoinductive property and improve MRI effect.

Synthesis of biodegradable and electroactive tetraaniline grafted poly(ester amide) copolymers for bone tissue engineering.

Biodegradable poly(ester amide)s have recently been used as biomaterials due to their desirable chemical and biological characteristics as well as their mechanical properties, which are amendable for material processing. In this study, electroactive tetraaniline (TA) grafted poly(ester amide)s were successfully synthesized and characterized. The poly(ester amide)s-graft-tetraaniline copolymers (PEA-g-TA) exhibited good electroactivity, mechanical properties, and biodegradability. The biocompatibility of the PEA-g-TA copolymers in vitro was systematically studied, which demonstrated that they were nontoxic and led to favorable adhesion and proliferation of mouse preosteoblastic MC3T3-E1 cells. Moreover, the PEA-g-TA copolymers stimulated by pulsed electrical signal could serve to promote the differentiation of MC3T3-E1 cells compared with TCPs. Hence, the biodegradable and electroactive PEA-g-TA copolymers possessed the properties in favor of the long-time potential application in vivo (electrical stimulation directly to the desired area) as bone repair scaffold materials in tissue engineering.

Sustained Delivery of Methylsulfonylmethane from Biodegradable Scaffolds Enhances Efficient Bone Regeneration.

Introduction: As a popular dietary supplement containing sulfur compound, methylsulfonylmethane (MSM) has been widely used as an alternative oral medicine to relieve joint pain, reduce inflammation and promote collagen protein synthesis. However, it is rarely used in developing bioactive scaffolds in bone tissue engineering. Methods: Three-dimensional (3D) hydroxyapatite/poly (lactide-co-glycolide) (HA/PLGA) porous scaffolds with different doping levels of MSM were prepared using the phase separation method. MSM loading efficiency, in vitro drug release as well as the biological activity of MSM-loaded scaffolds were investigated by incubating mouse pre-osteoblasts (MC3T3-E1) in the uniform and interconnected porous scaffolds. Results: Sustained release of MSM from the scaffolds was observed, and the total MSM release from 1% and 10% MSM/HA/PLGA scaffolds within 16 days was up to 64.9% and 68.2%, respectively. Cell viability, proliferation, and alkaline phosphatase (ALP) activity were significantly promoted by incorporating 0.1% of MSM in the scaffolds. In vivo bone formation ability was significantly enhanced for 1% MSM/HA/PLGA scaffolds indicated by the repair of rabbit radius defects which might be affected by a stimulated release of MSM by enzyme systems in vivo. Discussion: Finding from this study revealed that the incorporation of MSM would be effective in improving the osteogenesis activity of the HA/PLGA porous scaffolds.