Application of a Bioactive/Bioresorbable Three-Dimensional Porous Uncalcined and Unsintered Hydroxyapatite/Poly-d/l-lactide Composite with Human Mesenchymal Stem Cells for Bone Regeneration in Maxillofacial Surgery: A Pilot Animal Study

Abstract

A novel three-dimensional (3D) porous uncalcined and unsintered hydroxyapatite/poly-d/l-lactide (3D-HA/PDLLA) composite demonstrated superior biocompatibility, osteoconductivity, biodegradability, and plasticity, thereby enabling complex maxillofacial defect reconstruction. Mesenchymal stem cells (MSCs)—a type of adult stem cell—have a multipotent ability to differentiate into chondrocytes, adipocytes, and osteocytes. In a previous study, we found that CD90 (Thy-1, cluster of differentiation 90) and CD271 (low-affinity nerve growth factor receptor) double-positive cell populations from human bone marrow had high proliferative ability and differentiation capacity in vitro. In the present study, we investigated the utility of bone regeneration therapy using implantation of 3D-HA/PDLLA loaded with human MSCs (hMSCs) in mandibular critical defect rats. Microcomputed tomography (Micro-CT) indicated that implantation of a 3D-HA/PDLLA-hMSC composite scaffold improved the ability to achieve bone regeneration compared with 3D-HA/PDLLA alone. Compared to the sufficient blood supply in the mandibular defection superior side, a lack of blood supply in the inferior side caused delayed healing. The use of Villanueva Goldner staining (VG staining) revealed the gradual progression of the nucleated cells and new bone from the scaffold border into the central pores, indicating that 3D-HA/PDLLA loaded with hMSCs had good osteoconductivity and an adequate blood supply. These results further demonstrated that the 3D-HA/PDLLA-hMSC composite scaffold was an effective bone regenerative method for maxillofacial boney defect reconstruction.

Additive Manufacturing Methods for Producing Hydroxyapatite and Hydroxyapatite-Based Composite Scaffolds: A Review

“…As an illustration, 3D-printed HAp ceramics obtained by digital light processing showed the ability to improve the growth and proliferation of MC3 T3-E1 osteoblast precursor cell line as well as facilitate the cell adhesion and migration in vitro (Zeng et al, 2018). Furthermore, in vivo experimental studies have proven that 3Dprinted scaffolds made of HAp and its composites could act as excellent bone replacements, thanks to proper osteoconductivity (Cho et al, 2019b;Sha et al, 2019). It should be mentioned that 3D-printed HAp scaffolds are also found as competent vehicles to deliver osteogenic growth factors like bone morphogenetic protein-2 for improving in vivo bone regeneration (Chen G. et al, 2019).…”

Bone Regeneration Capacity of Newly Developed Uncalcined/Unsintered Hydroxyapatite and Poly-l-lactide-co-glycolide Sheet in Maxillofacial Surgery: An In Vivo Study

“…( B ) Placement of reconstructive material. ( C ) Site of sample taken for analysis (the orange vertical line) (image modified from Sha et al [ 18 ]). ( D ) Schematic coronal view of the specimen.…”

Restoration of FVIII Function and Phenotypic Rescue in Hemophilia A Mice by Transplantation of MSCs Derived From F8-Modified iPSCs

“…Mesenchymal stem cells -based therapy for various diseases has been in progress in clinical trials, including cardiovascular diseases ( Zhao et al, 2015 ; Bartolucci et al, 2017 ; Butler et al, 2017 ; Kim et al, 2018 ), neurodegenerative diseases ( Syková et al, 2017 ; Oh et al, 2018 ), and autoimmune diseases ( Ghoryani et al, 2019 ), which emphasizes the therapeutic effects of MSCs. Additionally, MSCs have been applied for tissue repair and regeneration ( Tan et al, 2016 ; Gjerde et al, 2018 ; Sha et al, 2019 ). Therefore, MSC-based therapy has been proven to be a safe and effective strategy.…”