Gelatin methacryloyl (GelMA) hydrogels is a widely used bioink because of its good biological properties and tunable physicochemical properties, which has been widely used in a variety of tissue engineering and tissue regeneration. However, pure GelMA is limited by the weak mechanical strength and the lack of continuous osteogenic induction environment, which is difficult to meet the needs of bone repair. Moreover, GelMA hydrogels are unable to respond to complex stimuli and therefore are unable to adapt to physiological and pathological microenvironments. This review focused on the functionalization strategies of GelMA hydrogel based bioinks for bone regeneration. The synthesis process of GelMA hydrogel was described in details, and various functional methods to meet the requirements of bone regeneration, including mechanical strength, porosity, vascularization, osteogenic differentiation, and immunoregulation for patient specific repair, etc. In addition, the response strategies of smart GelMA-based bioinks to external physical stimulation and internal pathological microenvironment stimulation, as well as the functionalization strategies of GelMA hydrogel to achieve both disease treatment and bone regeneration in the presence of various common diseases (such as inflammation, infection, tumor) are also briefly reviewed. Finally, we emphasized the current challenges and possible exploration directions of GelMA-based bioinks for bone regeneration.
Osteoarthritis (OA) is a highly prevalent whole-joint disease that causes disability and pain and affects a patient's quality of life. However, currently, there is a lack of effective early diagnosis and treatment. Although stem cells can promote cartilage repair and treat OA, problems such as immune rejection and tumorigenicity persist. Extracellular vesicles (EVs) can transmit genetic information from donor cells and mediate intercellular communication, which is considered a functional paracrine factor of stem cells. Increasing evidences suggest that EVs may play an essential and complex role in the pathogenesis, diagnosis, and treatment of OA. Here, we introduced the role of EVs in OA progression by influencing inflammation, metabolism, and aging. Next, we discussed EVs from the blood, synovial fluid, and joint-related cells for diagnosis. Moreover, we outlined the potential of modified and unmodified EVs and their combination with biomaterials for OA therapy. Finally, we discuss the deficiencies and put forward the prospects and challenges related to the application of EVs in the field of OA.
Emerging piezoelectric biomaterials have demonstrated their huge potential in diverse medical applications, including ultrasound diagnosis and tissue regeneration. Human body possesses inherent piezoelectricity, producing electrical signal under endogenous load or external pressure to modulate cellular behaviors. Tissue defects caused by traumatic injury will disrupt the electrophysiological microenvironment of the injured area, resulting in unenviable self‐healing. Triggered by physical activities or external stimulation, piezoelectric biomaterials exhibit a unique capability to generate electrical fields to restore the electrophysical microenvironment, reprogram cell fate and ultimately facilitate tissue repair. In this review, endogenous piezoelectric substances in the body and tissue piezoelectricity are introduced. Then, the characteristics and piezoelectricity of piezoelectric biomaterials in regenerative medicine are discussed, as well as strategies to prepare novel piezoelectric composites. Moreover, the molecular mechanisms for the piezoelectric effect on regulating tissue regeneration are systematically summarized. Recent advancements in piezoelectric biomaterials are comprehensively overviewed, including in the regeneration of bone, cartilage, skeletal muscles, tendon, skin, nerve, teeth and periodontal, myocardium, blood vessel and cornea tissues. Finally, the major challenges and future perspectives of piezoelectric biomaterials in regenerative medicine are proposed, hoping to boost the advancement in this promising scientific territory.
Implants made of titanium and its alloys are currently widely used in the human body. A series of surface modification methods developed nowadays enable titanium alloy implants to serve effectively in the human body for a long time. This paper reviews three different types of surface modification technologies for biomedical titanium alloys: physical, chemical, and biological, with particular attention to the assistance of these three technologies on the biological properties of titanium alloys. The physical method can change the surface morphology of titanium implants and prepare specific coatings for the implants, such as oxide films, bioactive molecules, drugs, etc. Chemical and biological surface modification technologies can minimize bacterial adhesion on the implant surface, improve the integration of soft tissue around the implant, prevent the occurrence of peri-implantitis, and accelerate the process of damage repair. An ideal titanium implant surface should balance the optimal surface morphology, chemical properties, and bionic characteristics to accelerate bone integration, enhance stability, and reduce peri-implant inflammation. Future research should focus on combining technologies, exploring interactions at the cellular and molecular levels, and conducting extensive in vitro and in vivo studies to verify the effectiveness and safety of modified surfaces. The progress in these fields will help overcome the existing limitations, improve the performance of implants, and obtain better clinical results.
Tissue engineering and regenerative medicine have emerged as crucial disciplines focused on the development of new tissues and organs to overcome the limitations of traditional treatments for tissue damage caused by accidents, diseases, or aging. Strontium ion (Sr2+) has garnered significant attention for its multifaceted role in promoting regeneration medicine and therapy, especially in bone tissue regeneration. Recently, numerous studies further confirm that Sr2+ also plays a critical in soft tissue regeneration. This review firstly summarizes the influence of Sr2+ on critical biological processes such as osteogenesis, angiogenesis, immune modulation, matrix synthesis, mineralization, and antioxidative defence mechanisms. Then details the classification, properties, advantages, and limitations of Sr-containing biomaterials (SrBMs). Additionally, this review extends to the current applications of SrBMs in regenerative medicine for diverse tissues, including bone, cartilage, skeletal muscle, dental pulp, cardiac tissue, skin, hair follicles, etc. Moreover, the review addresses the challenges associated with current SrBMs and provides insights for their future designing and applications in regenerative medicine.