Jian-Chih Chen

Ligament tears can strongly influence an individual’s daily life and ability to engage in physical activities. It is essential to develop artificial scaffolds for ligament repairs in order to effectively restore damaged ligaments. In this experiment, the objective was to evaluate fibrous membranes as scaffolds for ligament repair. These membranes were created through electrospinning using piezoelectric polyvinylidene fluoride (PVDF) composites, which contained 1 wt.% and 3 wt.% of copper-impregnated nanohydroxyapatite (Cu-nHA). The proposed electrospun membrane would feature an aligned fiber structure achieved through high-speed roller stretching, which mimics the properties of biomimetic ligaments. Nanoparticles of Cu-nHA had been composited into PVDF to enhance the pirzoelectric β-phase of the PVDF crystallines. The study assessed the physicochemical properties, antibacterial activity, and biocompatibility of the membranes in vitro. A microstructure analysis revealed that the composite membrane exhibited a bionic structure with aligned fibers resembling human ligaments. The piezoelectric performance of the experimental group containing 3 wt.% Cu-nHA was significantly improved to 25.02 ± 0.68 V/g·m⁻² compared with that of the pure PVDF group at 18.98 ± 1.18 V/g·m⁻². Further enhancement in piezoelectric performance by 31.8% was achieved by manipulating the semicrystalline structures. Antibacterial and cytotoxicity tests showed that the composite membrane inherited the antibacterial properties of Cu-nHA nanoparticles without causing cytotoxic reactions. Tensile tests revealed that the membrane’s flexibility of strain was adequate for use as artificial scaffolds for ligaments. In particular, the mechanical properties of the two experimental groups containing Cu-nHA were significantly enhanced compared with those of the pure PVDF group. The favorable piezoelectric and flexible properties are highly beneficial for ligament tissue regeneration. This study successfully developed PVDF/Cu-nHA piezoelectric fibers for a biocompatible, unidirectional piezoelectric membrane with potential applications as ligament repair scaffolds.

Calcium phosphate bone cement (CPC) is a popular material for bone remodeling, and nanohydroxyapatite (nHA) represents a breakthrough that has a wide range of clinical applications. During the early stages of bone repair, antibacterial and angiogenesis effects are essential to remodel new bone tissues. In this study, an antibacterial effect was achieved by incorporating Cu²⁺-doped nano-hydroxyapatite (Cu–nHA) synthesized through hydrothermal methods into CPC, and the impact of various amounts of Cu–nHA addition on the antibacterial and mechanical properties of CPC hybridization was evaluated. Moreover, the effects of Cu–nHA/CPC composites on the proliferation and mineralization of mouse progenitor osteoblastic cells (D1 cells) were characterized; the cell migration and angiogenesis ability of vascular endothelial cells (HUVECs) were also studied. Results indicated that incorporating 5 wt.% and 10 wt.% Cu–nHA into CPC led to a practical short-term antibacterial effect on S. aureus but not on E. coli. These Cu–nHA/CPC slurries remained injectable, anti-disintegrative, and non-toxic. Furthermore, compared with pure CPC, these Cu–nHA/CPC slurries demonstrated positive effects on D1 cells, resulting in better proliferation and mineralization. In addition, these Cu–nHA/CPC slurries were more effective in promoting the migration and angiogenesis of HUVECs. These findings indicate that 10 wt.% Cu–nHA/CPC has great application potential in bone regeneration.

Background: Minimally invasive plate osteosynthesis (MIPO) for clavicular shaft fracture yields favorable functional outcomes and results in less surgery-related soft tissue injury than other techniques. Anterior chest and shoulder skin numbness, a common complication after open reduction and plate fixation, is related to injury to the supraclavicular nerves. We propose MIPO combined with a mini-open approach without fluoroscopy for nerve preservation to minimize the risk of postoperative numbness compared with traditional open plating without nerve preservation. Methods: A total of 59 patients were retrospectively identified, with a follow-up period of 6 months. Thirty-two patients underwent MIPO with mini-open and nerve preservation technique (MIPO group), and 27 patients underwent traditional open plating without nerve preservation (open group). Constant–Murley shoulder outcome score, operation time, wound length, skin numbness, and number of implant removals were compared between the groups. Results: The MIPO group had significantly lower rates of anterior chest and shoulder skin numbness than the open group (MIPO: 12.5% vs. open: 55.6%; p < 0.001). Operation time was significantly longer in the MIPO group than in the open group (MIPO: 109.38 ± 18.83 vs. open: 81.48 ± 18.85; p < 0.001). Wound length was significantly shorter in the MIPO group than in the open group (MIPO: 4.73 ± 0.79 vs. open: 9.76 ± 1.64; p < 0.001). Both groups had similarly excellent Constant–Murley shoulder scores. There were significantly fewer implant removals in the MIPO group than in the open group (MIPO: 6.3% vs. open: 25.9%; p = 0.036). Neither group experienced any infection, implant failure, or nonunion. Conclusions: Our technique combining MIPO with the mini-open approach and supraclavicular nerve preservation yields a lower incidence of skin numbness than traditional open plating without nerve preservation.

The cornea lacks the ability to repair itself and must rely on transplantation to repair damaged tissue. Therefore, creating alternative therapies using dressing membranes based on tissue engineering concepts to repair corneal damage before failure has become a major research goal. Themost outstanding features that are important in reconstructing a damaged cornea are the mechanical strength and transparency of the membrane, which are the most important standard considerations. In addition, preventing infection is an important issue, especially in corneal endothelial healing processes. The purpose of this study was to produce aligned fibers via electrospinning technology using gelatin (Gel) composite polycaprolactone (PCL) as an optimal transport and antibiotic release membrane. The aim of the composite membrane is to achieve good tenacity, transparency, antibacterial properties, and in vitro biocompatibility. Results showed that the Gel and PCL composite membranes with the same electrospinning flow rate had the best transparency. The Gel impregnated with gentamicin antibiotic in composite membranes subsequently exhibited transparency and enhanced mechanical properties provided by PCL and could sustainably release the antibiotic for 48 h, achieving good antibacterial effects without causing cytotoxicity. This newly developed membrane has the advantage of preventing epidermal tissue infection during clinical operations and is expected to be used in the reconstruction of damaged cornea in the future.

This study aims to compare the anti-osteoporotic drugs alendronic acid (ALN) and flufenamic acid (FA) alone impregnate into nanoparticles of mesoporous bioactive glass (nMBG), which further composites calcium phosphate cement (CPC) and investigates their in vitro performance. The drug release, physicochemical properties, and biocompatibility of nMBG@CPC composite bone cement are tested, and the effect of the composites on improving the proliferation and differentiation efficiency of mouse precursor osteoblasts (D1 cells) is also investigated. Drug release shows that FA impregnates nMBG@CPC composite, a large amount of FA is released rapidly within 8 h, gradually reaching a stable release within 12 h, followed by a slow and sustained release within 14 days, and then reaches a plateau within 21 days. The release phenomenon confirms that the drug-impregnated nBMG@CPC composite bone cement effectively achieves slow drug delivery. The working time and setting time of each composite are within 4–10 min and 10–20 min, respectively, meeting the operational requirements of clinical applications. The addition of nMBG nanoparticles in the CPC matrix did not prevent the aggregation phenomenon under microstructural observation, thus resulting in a decrease in the strength of the nMBG@CPC composite. However, after 24 h of immersed reaction, the strength of each 5 wt.% nMBG impregnated with different concentrations of FA and ALN is still greater than 30 MPa, which is higher than the general trabecular bone strength. The drug-impregnated nMBG@CPC composites did not hinder the product formation and exhibit biocompatibility. Based on the proliferation and mineralization of D1 cells, the combination of nMBG with abundant FA and ALN in CPC is not conducive to the proliferation of D1 cells. However, when D1 cells are contact cultured for 21 days, alkaline phosphatase (ALP) enzyme activity shows higher ALP secretion from drug-impregnated nMBG@CPC composites than drug-free composites. Accordingly, this study confirms that nMBG can effectively impregnate the anti-osteoporosis drugs FA and ALN, and enhance the mineralization ability of osteoblasts. Furthermore, drug-impregnated nMBG applications can be used alone or in combination with CPC as a new option for osteoporotic bone-filling surgery.

Osteoarthritis (OA) is one of the most common diseases leading to physical disability, with age being the main risk factor, and degeneration of articular cartilage is the main focus for the pathogenesis of OA. Autophagy is a crucial intracellular homeostasis system recycling flawed macromolecules and cellular organelles to sustain the metabolism of cells. Growing evidences have revealed that autophagy is chondroprotective by regulating apoptosis and repairing the function of damaged chondrocytes. Then, OA is related to autophagy depending on different stages and models. In this review, we discuss the character of autophagy in OA and the process of the autophagy pathway, which can be modulated by some drugs, key molecules and non-coding RNAs (microRNAs, long non-coding RNAs and circular RNAs). More in-depth investigations of autophagy are needed to find therapeutic targets or diagnostic biomarkers through in vitro and in vivo situations, making autophagy a more effective way for OA treatment in the future. The aim of this review is to introduce the concept of autophagy and make readers realize its impact on OA. The database we searched in is PubMed and we used the keywords listed below to find appropriate article resources.

The objective of this study was to prepare hydroxyapatite (HA) with potential antibacterial activity against gram-negative and gram-positive bacteria by incorporating different atomic ratios of Cu²⁺ (0.1–1.0%), Mg²⁺ (1.0–7.0%), and Zn²⁺ (1.0–7.0%) to theoretically replace Ca²⁺ ions during the hydrothermal synthesis of grown precipitated HA nanorods. This study highlights the role of comparing different metal ions on synthetic nanoapatite in regulating the antibacterial properties and toxicity. The comparisons between infrared spectra and between diffractograms have confirmed that metal ions do not affect the formation of HA phases. The results show that after doped Cu²⁺, Mg²⁺, and Zn²⁺ ions replace Ca²⁺, the ionic radius is almost the same, but significantly smaller than that of the original Ca²⁺ ions, and the substitution effect causes the lattice distance to change, resulting in crystal structure distortion and reducing crystallinity. The reduction in the length of the nanopatites after the incorporation of Cu²⁺, Mg²⁺, and Zn²⁺ ions confirmed that the metal ions were mainly substituted during the growth of the rod-shape nanoapatite Ca²⁺ distributed along the longitudinal site. The antibacterial results show that nanoapatite containing Cu²⁺ (0.1%), Mg²⁺ (3%), and Zn²⁺ (5–7%) has obvious and higher antibacterial activity against gram-positive bacteria Staphylococcus aureus within 2 days. The antibacterial effect against the gram-negative bacillus Escherichia coli is not as pronounced as against Staphylococcus aureus. The antibacterial effect of Cu²⁺ substituted Ca²⁺ with an atomic ratio of 0.1~1.0% is even better than that of Mg²⁺- and Zn²⁺- doped with 1~7% groups. In terms of cytotoxicity, nanoapatites with Cu²⁺ (~0.2%) exhibit cytotoxicity, whereas Mg²⁺- (1–5%) and Zn²⁺- (~1%) doped nanoapatites are biocompatible at low concentrations but become cytotoxic as ionic concentration increases. The results show that the hydrothermally synthesized nanoapatite combined with Cu²⁺ (0.2%), Mg²⁺ (3%), and Zn²⁺ (3%) exhibits low toxicity and high antibacterial activity, which provides a good prospect for bypassing antibiotics for future biomedical applications.

Although considerable achievements have been made in the field of regenerative medicine, since self-repair is not an advanced ability of articular cartilage, the regeneration of osteochondral defects is still a challenging problem in musculoskeletal diseases. Cartilage regeneration aims to design a scaffold with appropriate pore structure and biological and mechanical properties for the growth of chondrocytes. In this study, porous scaffolds made of gelatin, hyaluronic acid, alginate, and sucrose in different proportions of 2 g (S_L2) and 4 g (S_L4) were used as porogens in a leaching process. Sucrose with particle size ranges of 88–177 μm (Hμ) and 44–74 μm (SHμ) was added to the colloid, and the individually cross-linked hydrogel scaffolds with controllable pore size for chondrocyte culture were named Hμ-S_L2, Hμ-S_L4, SHμ-S_L2 and SHμ-S_L4. The perforation, porosity, mechanical strength, biocompatibility, and proliferation characteristics of the hydrogel scaffold and its influence on chondrocyte differentiation are discussed. Results show that the addition of porogen increases the porosity of the hydrogel scaffold. Conversely, when porogens with the same particle size are added, the pore size decreases as the amount of porogen increases. The perforation effect of the hydrogel scaffolds formed by the porogen is better at 88–177 μm compared with that at 44–74 μm. Cytotoxicity analysis showed that all the prepared hydrogel scaffolds were non-cytotoxic, indicating that no cross-linking agent residues that could cause cytotoxicity were found. In the proliferation and differentiation of the chondrocytes, the SHμ-S_L4 hydrogel scaffold with the highest porosity and strength did not achieve the best performance. However, due to the compromise between perforation pores, pore sizes, and strength, as well as considering cell proliferation and differentiation, Hμ-SL4 scaffold provided a more suitable environment for the chondrocytes than other groups; therefore, it can provide the best chondrocyte growth environment for this study. The development of hydrogels with customized pore properties for defective cartilage is expected to meet the requirements of the ultimate clinical application.

Calcium phosphate bone cement (CPC) is in the form of a paste, and its special advantage is that it can repair small and complex bone defects. In the case of open wounds, tissue debridement is necessary before tissue repair and the subsequent control of wound infection; therefore, CPC composite hydrogel beads containing antibiotics provide an excellent option to fill bone defects and deliver antibiotics locally for a long period. In this study, CPC was composited with the millimeter-sized spherical beads of cross-linked gelatin–alginate hydrogels at the different ratios of 0 (control), 12.5, 25, and 50 vol.%. The hydrogel was impregnated with gentamicin and characterized before compositing with CPC. The physicochemical properties, gentamicin release, antibacterial activity, biocompatibility, and mineralization of the CPC/hydrogel composites were characterized. The compressive strength of the CPC/hydrogel composites gradually decreased as the hydrogel content increased, and the compressive strength of composites containing gentamicin had the largest decrease. The working time and setting time of each group can be adjusted to 8 and 16 min, respectively, using a hardening solution to make the composite suitable for clinical use. The release of gentamicin before the hydrogel beads was composited with CPC varied greatly with immersion time. However, a stable controlled release effect was obtained in the CPC/gentamicin-impregnated hydrogel composite. The 50 vol.% hydrogel/CPC composite had the best antibacterial effect and no cytotoxicity but had reduced cell mineralization. Therefore, the optimal hydrogel beads content can be 25 vol.% to obtain a CPC/gentamicin-impregnated hydrogel composite with adequate strength, antibacterial activity, and bio-reactivity. This CPC/hydrogel containing gentamicin is expected to be used in clinical surgery in the future to accelerate bone regeneration and prevent prosthesis infection after surgery.

Biomolecule grafting on polyether ether ketone (PEEK) was used to improve cell affinity caused by surface inertness. This study demonstrated the sequence-polished (P) and sulfonated (SA) PEEK modification to make a 3D structure, active biomolecule graftings through PEEK silylation (SA/SI) and then processed with phosphatidylcholine (with silylation of SA/SI/PC; without SA/PC) and type I collagen (COL I, with silylation of SA/SI/C; without SA/C). Different modified PEEKs were implanted for 4, 8, and 12 weeks for histology. Sulfonated PEEK of SA showed the surface roughness was significantly increased; after the silylation of SA/SI, the hydrophilic nature was remarkably improved. The biomolecules were effectively grafted through silylation, and the cells showed improved attachment after 1 h. Furthermore, the SA/SI/PC group showed good in vitro mineralization. The new bone tissues were integrated into the 3D porous structures of SA/SI/PC and SA/SI/C in vivo making PEEK a potential alternative to metals in orthopedic implants.