Growth factor-functionalized titanium implants for enhanced bone regeneration: A review.

Titanium and titanium alloys are widely favored materials for orthopedic implants due to their exceptional mechanical properties and biological inertness. The additional benefit of sustained local release of bioactive substances further promotes bone tissue formation, thereby augmenting the osseointegration capacity of titanium implants and attracting increasing attention in bone tissue engineering. Among these bioactive substances, growth factors have shown remarkable osteogenic and angiogenic induction capabilities. Consequently, researchers have developed various physical, chemical, and biological loading techniques to incorporate growth factors into titanium implants, ensuring controlled release kinetics. In contrast to conventional treatment modalities, the localized release of growth factors from functionalized titanium implants not only enhances osseointegration but also reduces the risk of complications. This review provides a comprehensive examination of the types and mechanisms of growth factors, along with a detailed exploration of the methodologies used to load growth factors onto the surface of titanium implants. Moreover, it highlights recent advancements in the application of growth factors to the surface of titanium implants (Scheme 1). Finally, the review discusses current limitations and future prospects for growth factor-functionalized titanium implants. In summary, this paper presents cutting-edge design strategies aimed at enhancing the bone regenerative capacity of growth factor-functionalized titanium implants-a significant advancement in the field of enhanced bone regeneration.

Progress of research on the surface functionalization of tantalum and porous tantalum in bone tissue engineering.

Tantalum and porous tantalum are ideal materials for making orthopedic implants due to their stable chemical properties and excellent biocompatibility. However, their utilization is still affected by loosening, infection, and peripheral inflammatory reactions, which sometimes ultimately lead to implant removal. An ideal bone implant should have exceptional biological activity, which can improve the surrounding biological microenvironment to enhance bone repair. Recent advances in surface functionalization have produced various strategies for developing compatibility between either of the two materials and their respective microenvironments. This review provides a systematic overview of state-of-the-art strategies for conferring biological functions to tantalum and porous tantalum implants. Furthermore, the review describes methods for preparing active surfaces and different bioactive substances that are used, summarizing their functions. Finally, this review discusses current challenges in the development of optimal bone implant materials.

17 variants interaction of Wnt/ß-catenin pathway associated with development of osteonecrosis of femoral head in Chinese Han population.

The genes of Wnt/ß-catenin pathway may have potential roles in fat accumulation of Non-traumatic osteonecrosis of the femoral head (ONFH), but the effects of their variants in the pathway on ONFH development have been remained unclear. To explore the potential roles of the variants in the development of ONFH, we completed the investigation of the paired interactions as well as their related biological functions of 17 variants of GSK3ß, LRP5, and FRP4 genes etc. in the pathway. The genotyping of the 17 variants were finished by MASS ARRAY PLATFORM in a 560 ONFH case-control system. The association of variants interactions with ONFH risk and clinical traits was evaluated by logistic regression analysis etc. and bioinformatics technology. The results showed that the genotype, allele frequency, and genetic models of Gsk3ß rs334558 (G/A), SFRP4 rs1052981 (A/G), and LRP5 rs312778 (T/C) were significantly associated with the increased and decreased ONFH risk and clinical traits, respectively (P < 0.001-0.0002). Particularly, the paired interactions of six variants as well as eight variants also showed statistically increased and decreased ONFH risk, bilateral hip lesions risk and stage IV risk of ONFH, respectively (P < 0.044-0.004). Our results not only at the first time simultaneously showed exact serum lipid disorder and abnormal platelet function of ONFH in the same study system with the 17 variants polymorphisms of Wnt/ß-catenin pathway but also shed light on the variants closely intervening the lipid disorder and abnormal coagulation of ONFH.

Emerging roles of growth factors in osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a potentially disabling orthopedic condition that requires total hip arthroplasty in most late-stage cases. However, mechanisms underlying the development of ONFH remain unknown, and the therapeutic strategies remain limited. Growth factors play a crucial role in different physiological processes, including cell proliferation, invasion, metabolism, apoptosis, and stem cell differentiation. Recent studies have reported that polymorphisms of growth factor-related genes are involved in the pathogenesis of ONFH. Tissue and genetic engineering are attractive strategies for treating early-stage ONFH. In this review, we summarized dysregulated growth factor-related genes and their role in the occurrence and development of ONFH. In addition, we discussed their potential clinical applications in tissue and genetic engineering for the treatment of ONFH.

Application of BMP in Bone Tissue Engineering.

At present, bone nonunion and delayed union are still difficult problems in orthopaedics. Since the discovery of bone morphogenetic protein (BMP), it has been widely used in various studies due to its powerful role in promoting osteogenesis and chondrogenesis. Current results show that BMPs can promote healing of bone defects and reduce the occurrence of complications. However, the mechanism of BMP in vivo still needs to be explored, and application of BMP alone to a bone defect site cannot achieve good therapeutic effects. It is particularly important to modify implants to carry BMP to achieve slow and sustained release effects by taking advantage of the nature of the implant. This review aims to explain the mechanism of BMP action in vivo, its biological function, and how BMP can be applied to orthopaedic implants to effectively stimulate bone healing in the long term. Notably, implantation of a system that allows sustained release of BMP can provide an effective method to treat bone nonunion and delayed bone healing in the clinic.

Sustained Release of VEGF to Promote Angiogenesis and Osteointegration of Three-Dimensional Printed Biomimetic Titanium Alloy Implants.

Tumor resection and treatment of trauma-related regional large bone defects have major challenges in the field of orthopedics. Scaffolds that treat bone defects are the focus of bone tissue engineering. 3D printing porous titanium alloy scaffolds, prepared via electron beam melting technology, possess customized structure and strength. The addition of a growth factor coating to the scaffold introduces a specific form of biological activation. Vascular endothelial growth factor (VEGF) is key to angiogenesis and osteogenesis in vivo. We designed a porous titanium alloy scaffold/thermosensitive collagen hydrogel system, equipped with VEGF, to promote local osseointegration and angiogenesis. We also verified the VEGF release via thermosensitive collagen and proliferation and induction of the human umbilical vein endothelial cells (HUVECs) via the composite system in vitro. In vivo, using microscopic computed tomography (Micro-CT), histology, and immunohistochemistry analysis, we confirmed that the composite scaffold aids in angiogenesis-mediated bone regeneration, and promotes significantly more bone integration. We also discovered that the composite scaffold has excellent biocompatibility, provides bioactive VEGF for angiogenesis and osteointegration, and provides an important theoretical basis for the restoration of local blood supply and strengthening of bone integration.