3D-Printed Hydrogels in Orthopedics: Developments, Limitations, and Perspectives.

Three-dimensional (3D) printing has been used in medical research and practice for several years. Various aspects can affect the finished product of 3D printing, and it has been observed that the impact of the raw materials used for 3D printing is unique. Currently, hydrogels, including various natural and synthetic materials, are the most biologically and physically advantageous biological raw materials, and their use in orthopedics has increased considerably in recent years. 3D-printed hydrogels can be used in the construction of extracellular matrix during 3D printing processes. In addition to providing sufficient space structure for osteogenesis and chondrogenesis, hydrogels have shown positive effects on osteogenic and chondrogenic signaling pathways, promoting tissue repair in various dimensions. 3D-printed hydrogels are currently attracting extensive attention for the treatment of bone and joint injuries owing to the above-mentioned significant advantages. Furthermore, hydrogels have been recently used in infection prevention because of their antiseptic impact during the perioperative period. However, there are a few shortcomings associated with hydrogels including difficulty in getting rid of the constraints of the frame, poor mechanical strength, and burst release of loadings. These drawbacks could be overcome by combining 3D printing technology and novel hydrogel material through a multi-disciplinary approach. In this review, we provide a brief description and summary of the unique advantages of 3D printing technology in the field of orthopedics. In addition, some 3D printable hydrogels possessing prominent features, along with the key scope for their applications in bone joint repair, reconstruction, and antibacterial performance, are discussed to highlight the considerable prospects of hydrogels in the field of orthopedics.

3D Printing for Bone-Cartilage Interface Regeneration.

Due to the vasculature defects and/or the avascular nature of cartilage, as well as the complex gradients for bone-cartilage interface regeneration and the layered zonal architecture, self-repair of cartilage and subchondral bone is challenging. Currently, the primary osteochondral defect treatment strategies, including artificial joint replacement and autologous and allogeneic bone graft, are limited by their ability to simply repair, rather than induce regeneration of tissues. Meanwhile, over the past two decades, three-dimension (3D) printing technology has achieved admirable advancements in bone and cartilage reconstruction, providing a new strategy for restoring joint function. The advantages of 3D printing hybrid materials include rapid and accurate molding, as well as personalized therapy. However, certain challenges also exist. For instance, 3D printing technology for osteochondral reconstruction must simulate the histological structure of cartilage and subchondral bone, thus, it is necessary to determine the optimal bioink concentrations to maintain mechanical strength and cell viability, while also identifying biomaterials with dual bioactivities capable of simultaneously regenerating cartilage. The study showed that the regeneration of bone-cartilage interface is crucial for the repair of osteochondral defect. In this review, we focus on the significant progress and application of 3D printing technology for bone-cartilage interface regeneration, while also expounding the potential prospects for 3D printing technology and highlighting some of the most significant challenges currently facing this field.

The combined effect of vitamin K and calcium on bone mineral density in humans: a meta-analysis of randomized controlled trials.

BACKGROUND: With the increasing incidence of osteoporosis, vitamin K and calcium have been linked to bone mineral density (BMD) and undercarboxylated osteocalcin (UcOC) in many studies, but the results of studies of the combined effect of vitamin K and calcium on BMD and UcOC in humans have been inconsistent. We conducted a systematic review of randomized controlled trials to assess the effect of this combination treatment on BMD and UcOC in humans. METHODS: A search for articles was conducted using PubMed, Embase, and the Cochrane Library database up to March 2021 (no language restrictions). We also reviewed the reference lists of the relevant publications and reviews to locate additional publications. The standard mean difference (SMD) was used as the primary measure of effect size. Our main endpoints were lumbar BMD, femoral neck BMD, hip BMD, total femoral BMD, and UcOC from baseline to end point. We performed subgroup analysis, heterogeneity testing, and assessment of publication bias. RESULTS: A total of 1346 patients from 10 randomized controlled trials were included in the meta-analysis. The forest plot analysis revealed that vitamin K combined with calcium was associated with a higher lumbar spine BMD compared to controls. The SMD was 0.20 [95% confidence interval (CI): 0.07 to 0.32]. Vitamin K and calcium supplementation led to a significant decrease in UcOC (SMD: - 1.71, 95% CI: - 2.45 to - 0.96). Subgroup analysis showed that vitamin K2 and vitamin K1 had SMDs of 0.30 (95% CI: 0.10 to 0.51) and SMDs of 0.14 (95% CI: - 0.02 to 0.29), and calcium dosages of ≤ 1000 mg/d or > 1000 mg/d had SMDs of 0.19 (95% CI: 0.05 to 0.32) and 0.26 (95% CI: - 0.04 to 0.55). CONCLUSION: The combination of vitamin K and calcium has a positive effect on lumbar BMD and decreases the level of UcOC. Registration: The protocol for this meta-analysis was registered at the International Prospective Register of Systematic Reviews (CRD42021251825).

The Association Between the Concentration of Serum Magnesium and Postmenopausal Osteoporosis.

Background: Osteoporosis is the most common and widespread chronic skeletal metabolic disease in the world and can lead to catastrophic fractures. Therefore, it is important to look for factors that can be modified or controlled to prevent osteoporosis. Although serum Mg is believed to be associated with osteoporosis in many individuals, there are conflicting reports on the association between serum Mg and osteoporosis. Therefore, this meta-analyses aimed to explore the association between the concentration of serum Mg and osteoporosis as well as that between the concentration of serum Mg and osteopenia. Methods: Articles were searched in PubMed. We also reviewed the reference lists of the relevant publications and reviews as of December 2019. Finally, 11 eligible studies involving 2,776 postmenopausal women were selected. We performed subgroup analysis, and publication bias was assessed. Results: According to the forest plot analysis, postmenopausal women with osteoporosis had a lower concentration of serum Mg than normal controls [standardized mean difference (SMD) = -0.56, 95% confidence interval (CI) = -1.02 to -0.09]. However, this result was not applicable to those with osteopenia (SMD = -0.30, 95% CI = -0.69 to 0.09). The subgroup analysis by geographical location found a similar pattern in European postmenopausal women with osteoporosis (SMD = -0.73, 95% CI = -1.322 to -0.143), but not in Asian (SMD = -0.007, 95% CI = -0.381 to 0.394). The subgroup analysis by site of bone mineral density (BMD) showed the serum Mg concentration of postmenopausal women with osteoporosis (BMD of femur) was lower than in healthy controls (SMD = -0.44, 95% CI = -0.77 to -0.12), and BMD of the spine group had the same conclusion (SMD = -0.78, 95% CI = -1.36 to -0.19). Besides, the serum Mg concentration of postmenopausal women with osteoporosis was lower than that of the normal bone mass group in the studies those included more than 50 postmenopausal women with osteoporosis (SMD = -0.57, 95% CI = -1.04 to -0.11). We also found postmenopausal women under the age of 60 with osteoporosis had a lower concentration of serum Mg than the healthy controls (SMD = -0.61, 95% CI = -1.09 to -0.13). Conclusion: Postmenopausal women with osteoporosis have a lower concentration of serum Mg. However, the association between the concentration of serum Mg and osteopenia needs further confirmation.

The relationship between serum vitamin D and fracture risk in the elderly: a meta-analysis.

BACKGROUND: The incidence of osteoporotic fractures has increased rapidly, and because of the poor prognosis and high mortality associated with osteoporotic fractures, they remain a prospective research area globally. One way to reduce their incidence is to investigate their intervention risk factors in the elderly. Hence, this study explores the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels and osteoporotic fractures in elderly patients through a meta-analysis. METHODS: We conducted our literature search mainly in PubMed and Embase for identifying studies that investigated the relationship between serum 25(OH)D levels and the risk for osteoporotic fractures. We performed categorical analysis, heterogeneity checks, publication bias analysis, and subgroup analyses. RESULTS: In total, 20 studies were included, of which 4 were case-cohort studies and 16 were cohort studies. A total of 41,738 patients from 20 studies were included in the meta-analysis, of which 5916 had fractures, including 3237 hip fractures. By combining the lowest and highest categories of relative risks (RRs) and 95% confidence intervals (CIs), it was suggested that lower serum 25-hydroxyvitamin D levels may be a risk factor for fractures. RR (95% CI) for total and hip fractures were 1.11 (0.99, 1.24) and 0.89 (0.80, 0.98) after adjustments. CONCLUSIONS: Our study showed that compared to low serum 25(OH)D levels, high serum 25(OH)D levels reduce the risk of hip fractures in the patients aged 60 years or older. In contrast, serum 25(OH)D has no significant relationship with total fracture risk.