About 6 million bone fractures occur annually in the US; 30% require bone grafting transplants to aid bone healing. Well-established clinical therapy techniques for bone regeneration suffer from limited availability, higher infection risk, donor site morbidity, and poor transplant integration. Delay in healing or nonunion of critical-sized defects is another concern in orthopedics. This dissertation focuses on constructing an interlocking scaffold structure to speed bone regeneration. In this thesis, a BMP-2 & 7 coated PCL-nanoclay-hydroxyapatite interlocking scaffold was developed to accelerate bone regeneration. Developed nano clay polymer interlocking scaffolds retain the scaffold's structural integrity and provide a large surface area while allowing for media interaction. Mesenchymal stem cells (MSCs) and osteoblast cells seeded at a 1:1 ratio boost cell viability and enable calcium deposition on day three and collagen production on day 7 with BMP-2 and BMP-7 coated scaffolds. In addition, BMPs, interlocking, and co-culturing of osteoblasts and MSCs promote osteogenic differentiation. In this dissertation, The long-term effect of BMP-2/BMP-7 on in-vitro utilizing interlocking scaffold blocks was evaluated. Changes to the nanomechanical properties of scaffolds and bone tissue during osteogenesis with the progression of ECM formation were reported. Gene expression results and Alizarin Red S staining images indicate a significant increase in mineralized bone nodules with BMPs coated samples compared with uncoated samples. Results suggest BMPs played a critical role in mineralized ECM production, which increased the scaffolds' elastic modulus. This research provides valuable insight into understanding how BMPs affect bone growth. In this dissertation, polymer clay nanocomposites fibers were constructed utilizing a pressured gyration setup and observed improved cell viability, osteogenic differentiation, ECM development, and collagen formation for PCL HAP MMT-Clay nanocomposite fiber scaffolds compared to pure PCL fibers. In this dissertation, the in-silico design of the unnatural amino acids modified clays and fabricated unnatural amino acids modified scaffolds were reported for application as cancer testbeds. This dissertation also reported the design of the in situ hydroxy apatite and tri-calcium phosphate incorporated nano clays polymer scaffolds for bone tissue engineering applications. These studies represent a new opportunity to design manufacturable composite nanoclay polymer scaffolds for bone tissue engineering applications.