Mineralized collagen (MC) is the basic unit of bone structure and function and is the main component of the extracellular matrix (ECM) in bone tissue. In the biomimetic method, MC with different nanostructures of neo-bone have been constructed. Among these, extra-fibrous MC has been approved by regulatory agencies and applied in clinical practice to play an active role in bone defect repair. However, in the complex microenvironment of bone defects, such as in blood supply disorders and infections, MC is unable to effectively perform its pro-osteogenic activities and needs to be functionalized to include osteogenesis and the enhancement of angiogenesis, anti-infection, and immunomodulation. This article aimed to discuss the preparation and biological performance of MC with different nanostructures in detail, and summarize its functionalization strategy. Then we describe the recent advances in the osteo-inductive properties and multifunctional coordination of MC. Finally, the latest research progress of functionalized biomimetic MC, along with the development challenges and future trends, are discussed. This paper provides a theoretical basis and advanced design philosophy for bone tissue engineering in different bone microenvironments.

The growth plate is a cartilaginous tissue with three distinct zones. Resident chondrocytes are highly organized in a columnar structure, which is critical for the longitudinal growth of immature long bones. Once injured, the growth plate may potentially be replaced by bony bar formation and, consequently, cause limb abnormalities in children. It is well-known that the essential step in growth plate repair is the remolding of the organized structure of chondrocytes. To achieve this, we prepared an anatomy-inspired bionic Poly(ε-caprolactone) (PCL) scaffold with a stratified structure using three-dimensional (3D) printing technology. The bionic scaffold is engineered by surface modification of NaOH and collagen Ⅰ (COL Ⅰ) to promote cell adhesion. Moreover, chondrocytes and bone marrow mesenchymal stem cells (BMSCs) are loaded in the most suitable ratio of 1:3 for growth plate reconstruction. Based on the anatomical structure of the growth plate, the bionic scaffold is designed to have three regions, which are the small-, medium-, and large-pore-size regions. These pore sizes are used to induce BMSCs to differentiate into similar structures such as the growth plate. Remarkably, the X-ray and histological results also demonstrate that the cell-loaded stratified scaffold can successfully rebuild the structure of the growth plate and reduce limb abnormalities, including limb length discrepancies and angular deformities in vivo. This study provides a potential method of preparing a bioinspired stratified scaffold for the treatment of growth plate injuries.

Bisphosphonates (BPs), the stable analogs of pyrophosphate, are well-known inhibitors of osteoclastogenesis to prevent osteoporotic bone loss and improve implant osseointegration in patients suffering from osteoporosis. Compared to systemic administration, BPs-incorporated coatings enable the direct delivery of BPs to the local area, which will precisely enhance osseointegration and bone repair without the systemic side effects. However, an elaborate and comprehensive review of BP coatings of implants is lacking. Herein, the cellular level (e.g., osteoclasts, osteocytes, osteoblasts, osteoclast precursors, and bone mesenchymal stem cells) and molecular biological regulatory mechanism of BPs in regulating bone homeostasis are overviewed systematically. Moreover, the currently available methods (e.g., chemical reaction, porous carriers, and organic material films) of BP coatings construction are outlined and summarized in detail. As one of the key directions, the latest advances of BP-coated implants to enhance bone repair and osseointegration in basic experiments and clinical trials are presented and critically evaluated. Finally, the challenges and prospects of BP coatings are also purposed, and it will open a new chapter in clinical translation for BP-coated implants.

Lee HW, et al. Clin Orthop Surg. 2022 Aug;14:e59. https://doi.org/10.4055/cios21191

Background: Bionic surface nanopatterns of titanium (Ti) materials have excellent antibacterial effects in vitro for infection prevention. To date, there is a lack of knowledge about the in vivo bactericidal outcomes of the nanostructures on the Ti implant surfaces. Methods: A systematic review was performed using the PubMed, Embase, and Cochrane databases to better understand surface nanoscale patterns’ in vivo antibacterial efficacy. The inclusion criteria were preclinical studies (in vivo) reporting the antibacterial activity of nanopatterns on Ti implant surface. Ex vivo studies, studies not evaluating the antibacterial activity of nanopatterns or surfaces not modified with nanopatterns were excluded. Results: A total of five peer-reviewed articles met the inclusion criteria. The included studies suggest that the in vivo antibacterial efficacy of the nanopatterns on Ti implants’ surfaces seems poor. Conclusions: Given the small number of literature results, the variability in experimental designs, and the lack of reporting across studies, concluding the in vivo antibacterial effectiveness of nanopatterns on Ti substrates’ surfaces remains a big challenge. Surface coatings using metallic or antibiotic elements are still practical approaches for this purpose. High-quality preclinical data are still needed to investigate the in vivo antibacterial effects of the nanopatterns on the implant surface.

Imbalances in the osteogenic–osteoclastic microenvironment hinder effective osseointegration between the prosthesis and host bone, which is a key factor contributing to the high incidence of prosthesis loosening and periprosthetic fractures in osteoporosis patients. Developing an implant interface that can reverse the dysregulated osteogenic microenvironment is an effective strategy to address this challenge. A novel bioinspired interface with a spatial gradient structure was engineered by 3D-printed porous titanium alloy implants and hollow mesoporous silica nanoparticles coating. Apart from the bioinspired bone microstructure, the amine-functionalized nanocoating of the bioactive interface could also load and temporally sustain the zoledronic acid (ZOL) release. A series of in vitro experiments were carried out to characterize the bioactive interface and to clarify the regulation of osteogenic–osteoclastic balance by ZOL temporal release from the nanocoatings. Afterward, an osteoporotic model was utilized to validate the in vivo bioactive interface osseointegration effect. Based on the structural features and chemical properties of the bioactive interface, efficient ZOL loading was achieved. Additionally, the temporal release mechanism of ZOL through free diffusion and ionic bond ionization enabled long-term sustained release. Meanwhile, the early high-concentration local release of ZOL effectively inhibited osteoclast formation and activation in the microenvironment. As the ZOL release decreased over time, the focus shifted to promoting the process of bone formation, thereby reversing the dysregulated osteogenic microenvironment. According to this, we identified the optimal gradient concentration (10^-5M) of the ZOL temporal release system that efficiently exerts bidirectional regulatory effects. Most notably, the spatial gradient structured interface loaded with this optimal concentration of ZOL (10^-5M) significantly augmented osseointegration under in vivo osteoporotic conditions. Overall, our study provides a novel nanocoating capable of temporally releasing ZOL to reverse the dysregulated osteogenic microenvironment, aiming to maintain the long-term stability of artificial prostheses for osteoporosis patients. This study validates the structure–performance-effect relationship of ZOL-releasing nanocoatings with a temporal release mechanism, providing a novel approach to addressing the high incidence of postoperative complications in osteoporotic patients undergoing prosthetic replacement.