Bone defects and fractures present significant clinical challenges, particularly in orthopedic and maxillofacial applications. While minor bone defects may be capable of healing naturally, those of a critical size necessitate intervention through the use of implants or grafts. The utilization of traditional methodologies, encompassing autografts and allografts, is constrained by several factors. These include the potential for donor site morbidity, the restricted availability of suitable donors, and the possibility of immune rejection. This has prompted extensive research in the field of bone tissue engineering to develop advanced synthetic and bio-derived materials that can support bone regeneration. The optimal bone substitute must achieve a balance between biocompatibility, bioresorbability, osteoconductivity, and osteoinductivity while simultaneously providing mechanical support during the healing process. Recent innovations include the utilization of three-dimensional printing, nanotechnology, and bioactive coatings to create scaffolds that mimic the structure of natural bone and enhance cell proliferation and differentiation. Notwithstanding the advancements above, challenges remain in optimizing the controlled release of growth factors and adapting materials to various clinical contexts. This review provides a comprehensive overview of the current advancements in bone substitute materials, focusing on their biological mechanisms, design considerations, and clinical applications. It explores the role of emerging technologies, such as additive manufacturing and stem cell-based therapies, in advancing the field. Future research highlights the need for multidisciplinary collaboration and rigorous testing to develop advanced bone graft substitutes, improving outcomes and quality of life for patients with complex defects.

Intrinsically conducting polymers (ICPs) are widely used to fabricate biomaterials; their application in neural tissue engineering, however, is severely limited because of their hydrophobicity and insufficient mechanical properties. For these reasons, soft conductive polymer hydrogels (CPHs) are recently developed, resulting in a water-based system with tissue-like mechanical, biological, and electrical properties. The strategy of incorporating ICPs as a conductive component into CPHs is recently explored by synthesizing the hydrogel around ICP chains, thus forming a semi-interpenetrating polymer network (semi-IPN). In this work, a novel conductive semi-IPN hydrogel is designed and synthesized. The hybrid hydrogel is based on a poly(N-isopropylacrylamide-co-N-isopropylmethacrylamide) hydrogel where polythiophene is introduced as an ICP to provide the system with good electrical properties. The fabrication of the hybrid hydrogel in an aqueous medium is made possible by modifying and synthesizing the monomers of polythiophene to ensure water solubility. The morphological, chemical, thermal, electrical, electrochemical, and mechanical properties of semi-IPNs were fully investigated. Additionally, the biological response of neural progenitor cells and mesenchymal stem cells in contact with the conductive semi-IPN was evaluated in terms of neural differentiation and proliferation. Lastly, the potential of the hydrogel solution as a 3D printing ink was evaluated through the 3D laser printing method. The presented results revealed that the proposed 3D printable conductive semi-IPN system is a good candidate as a scaffold for neural tissue applications.