Bone Growth Capacity of Human Umbilical Cord Mesenchymal Stem Cells and BMP-2 Seeded Into Hydroxyapatite/Chitosan/Gelatin Scaffold in Alveolar Cleft Defects: An Experimental Study in Goat

Abstract

Objective: To evaluate bone regeneration in alveolar defects treated with human umbilical cord–derived mesenchymal stem cells (hUCMSCs), hydroxyapatite/chitosan/gelatin (HA/CS/Gel) scaffold, and bone morphogenic protein-2 (BMP-2) in Capra hircus models. Design: Randomized posttest-only control group design. Setting: Animal Hospital at Bogor Agricultural Institute. Participants: Healthy and equally treated 24 female Capra hircus/goats. Intervention: Animals were randomly assigned to 3 experimental group design (iliac crest alveolar bone graft/ICABG [control], HA/Cs/Gel+BMP-2 [ Novosys], and HA/Cs/Gel+BMP-2+UCMSCs). Graft materials were implanted in surgically made alveolar defects. Main Outcome Measures: Postoperative functional score and operating time were assessed. New bone growth, bone density, inflammatory cells recruitment, and neoangiogenesis were evaluated based on radiological and histological approach at 2 time points, week 4 and 12. Statistical analysis was done between treatment groups. Results: Operating time was 34% faster and functional score 94.5% more superior in HA/Cs/Gel+BMP-2+hUCMSC group. Bone growth capacity in HA/Cs/Gel+BMP-2+UCMSCs mimicked ICABG, but ICABG showed possibility of bone loss between week 4 and 12. The HA/Cs/Gel+BMP-2+UCMSCs showed early bone repopulation and unseen inflammatory cells and angiogenesis on week 12. Discussion and Conclusion: The HA/Cs/Gel+BMP-2+hUCMSCs were superior in enhancing new bone growth without donor site morbidity compared to ICABG. The presence of hUCMSCs in tissue-engineered alveolar bone graft (ABG), supported with paracrine activity of the resident stem cells, initiated earlier new bone repopulation, and completed faster bone regeneration. The HA/Cs/Gel scaffold seeded with UCMSCs+BMP-2 is a safe substitute of ICABG to close alveolar bone defects suitable for patients with cleft lip, alveolus, and palate.

Mesenchymal Stem Cell Studies in the Goat Model for Biomedical Research—A Review of the Scientific Literature

“…Stem cell research in dentistry aims at the regeneration of damaged tissues such as periodontal tissues, dentin, pulp, and resorbed roots and the repair of endodontic iatrogenic perforations [ 142 ]. It is mainly used for periodontal regeneration and in association with biomaterials to optimize tooth regeneration in the goat model [ 143 , 144 ]. Undifferentiated MSCs are able to differentiate, providing the three critical tissues essential for periodontal tissue regeneration: cementum, bone, and periodontal ligaments, making stem cells a new approach for periodontal tissue regeneration [ 145 ].…”

“…Nevertheless, the absence of periodontal ligament and connective tissue results in important differences in implant adaptation to occlusal forces [ 145 ]. Several studies for tooth regeneration with scaffolds based on biomaterials and stem cells have shown very positive effects on regeneration [ 143 , 144 , 145 , 147 ]. Dense collagen gel scaffolds seeded on MSCs and nanostructured titanium surfaces have increased interest in bone regeneration due to the good osteointegration effect [ 148 , 149 ].…”

“…Bangun et al (2021) proved that MSCs can improve earlier bone repopulation and complete faster bone regeneration in tissue-engineered bone grafts, supported by the paracrine activity of the resident stem cells [ 144 ].…”

Tissue Engineering in Stomatology: A Review of Potential Approaches for Oral Disease Treatments

“…Oral and maxillofacial bone defects are diseases caused by congenital deformity, trauma, tumors, inflammation, or periodontal disease and mainly include alveolar, maxillary, and mandibular bone defects ( Bangun et al, 2021 ; Lin and Kudva, 2021 ). Bone transplantation, guided bone regeneration membrane technology, stimulation of osteogenesis, and prosthetic repair are the main methods for the healing of defects.…”

Chitosan as Bone Scaffold for Craniofacial Bone Regeneration: A Systematic Review

“…Chitosan is a natural biopolymer that is very versatile as a biological material to help the healing process of soft and hard connective tissue [7]. Some studies show chitosan or combination of chitosan with other active materials have positive impact for bone regeneration [8], [9], [10]. In this systematic review, we aim to explore the recent literature regarding chitosan as a bone scaffold for craniofacial bone regeneration.…”