Towards tissue engineering application for cleft defects
Authors:   , Natsir Kalla Diandra Sabrina 
Published: September 2023

The main objective of this thesis was to investigate the current clinical practice and associated difficulties in treating cleft lip and palate, the state-of-the-art tissue engineering techniques for the reconstruction of oral clefts, and to assess the safety and efficacy of novel tissue engineering approaches for alveolar cleft defects.
In Chapter 2, we compared the costs and complication rates of Secondary Alveolar Bone Grafting (SABG) outcomes in alveolar cleft patients treated either in daycare or with multiple day hospitalization (MDH). Daycare had marginally, but not substantially, higher rates of complications, the majority of which were classified by Clavien Dindo as Grade I (mild). According to the study, daycare after alveolar cleft surgery is about as safe as MDH, although much less expensive.
In Chapter 3, we investigated intraoperative and early postoperative blood loss using the buccal fat pad (BFP) during cleft lip and/or cleft palate (CL/P) surgery that resulted in weight, and the procedure length can cause more blood loss during palatoplasty, which suggests that younger patients will have better results from their procedures.
In Chapter 4, we conducted a systematic review and meta-analysis to assess the effectiveness of stem cell-based tissue engineering for the treatment of alveolar cleft (AC) and cleft palate (CP) deformities in animal models, which concluded that adding cells to biomaterials improves AC and CP reconstructions.
In Chapter 5, a second systematic review and meta-analysis of controlled clinical trials utilizing regeneration materials for alveolar cleft repairs was carried out. The review also took the risk of bias (RoB) into account. According to the meta-analysis, the regenerative materials and iliac crest grafts did not differ significantly. Additionally, this review's findings indicated that control trials' high RoB indicated the need for quality improvement in control trials.
In Chapter 6, we presented a clinical trial protocol to assess the feasibility and safety of a novel calcium-polyphosphate-complexed bone-inducing graft material for alveolar cleft reconstructions known as Ca-polyP microparticles (Ca-polyP MPs). Following the trial's conclusion, the findings regarding safety, feasibility, and bone formation using polyP as a graft material will be published.
In Chapter 7, we described in great detail the outcomes of a single-blinded, parallel, prospective clinical pilot research using Ca-polyP MPs for alveolar cleft repairs with 8 adolescent patients (ages 13 to 34), of which the protocol was described in Chapter 6. Our research showed that both transplants may be used safely. However, compared to Ca-polyP alone, the combination of Ca-polyP + BCP graft demonstrated more excellent stability in alveolar cleft reconstruction, as measured by the Bergland scale. It is advised that future clinical trials include a bigger sample size.
In Chapter 8, we presented a clinical trial design to assess the viability and safety of combining biphasic calcium phosphate (BCP) with microfragmented fat (MFAT) for alveolar cleft repairs. This prospective, non-blinded, first-in-human clinical research will include eight patients with alveolar clefts. Regardless of the trial's findings, the safety, feasibility, and efficacy of the BCP-MFAT combination in promoting bone formation will be disclosed.
In Chapter 9, we described in detail the results of a first-in-man prospective non-blind clinical pilot study of alveolar cleft reconstructions using a BCP-MFAT combination, which included 8 adult patients. No local or systemic side effects, allergic reactions, or other adverse events were noticed. The Bergland scale had radiographic examinations from I through III. In summary, the BCP-MFAT grafts seem to be secure and practical for alveolar cleft reconstruction.