## 4 Discussion
### Cell Therapy  
Seeding scaffolds with biologically active cells in order to promote bone regeneration directly at the implant site is a commonly employed bone tissue engineering strategy. All the studies with scaffolds serving as carriers for MSCs reported an increased bone formation compared to scaffold-only cohorts [23; 26; 34; 39; 71; 81; 82; 85; 98; 106]. Scaffolds can function as a substitute for native ECM for the conduction, attachment, and growth of encapsulated MSCs cells and prevent anoikis, a form of apoptosis [10]. Furthermore, scaffolds are optimized to protect against host immune attack and induce major cellular processes that are necessary for tissue regeneration [10]. The most commonly used cell therapy used the bone-marrow-derived MSCs (BMSCs), which are capable of differentiating multiple mesodermal lineages, including bone and cartilage [23]. [PERSON] et al. [23] investigated the bioactivity of an n-HA/PA composite implant seeded with ectogenic BMSCs and found that ectogenic BMSCs had a significant impact on bone regeneration in bone-marrow-poor locations such as mandible angle. The authors suggested that the presence of endogenic BMSCs at the implantation site was found to be a critical factor in determining the outcome of the bone regeneration process, since ectogenic BMSCs were not found to enhance bone regeneration in the rich-marrow sites such as the mandibular body, implicating different tissue engineering strategies for bone defects in marrow-rich and marrow-poor sites. Dental pulp stem cells (DPSCs) offer certain advantages over other SCs, such as accessibility, availability and multipotency, maintain an undifferentiated state upon long-term cultivation, and are little influenced by the number of passages [146]. [PERSON] et al. [26] reported HA/PLGA/DPSCs scaffolds without offering improved bone regeneration due to significant differences in the mRNA levels of osteogenic markers capable of determining osteoblastic stage differentiation (Runx2, OPN, COL1, and ALP). Adipose-derived SCs (ADSCs) have certain advantages compared to BMSCs, such as easy harvesting, a huge number of cells can be obtained from fat tissue, cells that are easy to cultivate and a higher proliferation capacity [147]. [PERSON] et al. [35] found that ADSCs seeding on ceramic/polymer scaffolds improve bone regeneration in large mandibular defects and results in significantly higher bone volume and an increased amount of osteoclast deposition. The combination of MSCs with BMP-2 and composite ceramic/polymer scaffolds resulted in significantly more bone regeneration than when using MSCs/scaffold and BMP-2/scaffold complexes [25; 28; 43; 49]. Local gene therapy using BMPs transfected on MSCs and porous n-HA/PA scaffolds in the repair of mandibular defects in rabbits, as well as their response during various periods, showed good biocompatibility, more significant bone formation and earlier mineralization in the implant area. BMP7-transfected MSCs resulted in significantly higher-end elastic modulus, ultimate stress, and ultimate strain four weeks after implantation of the mandibular explant [28]. In addition, no differences were observed between the MSC-only and BMP7-transfected MSC groups at 16 weeks, implying that BMP-7 enhances bone formation in the early phases of mandibular bone regeneration [28]. However, in a study investigating the efficacy of PLGA scaffolds, alone and in combination with BMP-2 and MSCs, when healing a critical-sized segmental mandibular defect in a rat model, bone regeneration was most robust in the BMP-2-treated scaffolds [40]. In this study, bone regeneration scores were graded according to a previously described semi-quantitative scale based on micro-CT images without histological examination. In a study that compared liposome-mediated gene transfer with MSCs and adenoviral-mediated MSC transduction with BMP-2, the authors found that adenovirus-transfected MSCs resulted in nearly complete bone healing within four weeks of the scaffold being implanted [61].