Polymer/nano-hydroxyapatite 3D aerogel scaffolds: a novel scaffold for bone regeneration

Abstract

Abstract of the thesis entitled Polymer/nano-hydroxyapatite 3D aerogel scaffolds: A novel scaffold for bone regeneration Submitted by MA Muzhi for the degree of Doctor of Philosophy at the University of Hong Kong in March 2021 Bone regeneration using scaffold is useful to restore jaw bone defects for reconstruction and dental implant placement. A novel aerogel scaffold made from poly-L-lactic acid (PLLA) and nano-hydroxyapatite (nHAp) was developed through a solvent replacement freeze-drying technology. This study investigated the physical properties and degradation process of PLLA/nHAp aerogels of different amounts of nHAp, and also investigated qualitatively the adhesion, growth, migration, proliferation and osteogenic differentiation of Adipose-derived mesenchymal stem cells (ADMSCs) on the PLLA / nHAp aerogel scaffold in an in vitro setting. A high porosity (89-93%) was noted in the structure of the PLLA aerogel scaffold, and the introduction of nHAp significantly increased the mechanical properties (highest compressive modulus was 8.5MPa for 30/70 PLLA/nHAp and the highest tensile strength was 1.42MPa for 50/50 PLLA/nHAp). The water contact angle of the original PLLA scaffold was 92°, while a lower angle was measured (~46–73°) when the nHAp were incorporated. ADMSCs were obtained and cultured with different mixture ratio of PLLA/nHAp nanostructured aerogel scaffolds. The macroscopic and histopathological observations were performed to assess the osteogenesis potential. Bone formation was more obvious in the ADMSCs-50/50 PLLA/nHAp aerogel scaffolds group than the other groups (P < 0.05). Alkaline phosphatase (ALP) activity and osteopontin (OPN) secretion as early and late markers for osteoblastic differentiation were significantly increased in the ADMSCs-PLLA/nHAp aerogel scaffolds groups. Hence, the novel PLLA/ nHAp aerogel scaffolds have potential for bone tissue engineering. Aerogel scaffolds were prepared using solvent replacement freeze-drying techniques. 6 mm calvarial critical-sized defects were created on the midline. Sixty-four defects were covered with different aerogel scaffolds (pure PLLA, 70/30 and 50/50 PLLA/nHAp) or without any treatment as a blank control. Micro-CT and histological methods were performed four weeks and eight weeks to explore bone regeneration. The data was analysed with Student’s t-test. Micro-CT three-dimensional (3D) reconstruction showed that there were significant differences (P<0.05) in bone volume (BV) and bone volume relative to tissue volume (BV/TV) among all groups, and both values of the 50/50 PLLA/nHAp group was the highest and had the most substantial amount of bone formation. H&E staining showed that bone regeneration of the PLLA/nHAp groups was better than the pure PLLA group, and the 50/50 PLLA/nHAp group had the best repair effect on the cranial defect. Ultimately, PLLA/nHAp aerogel scaffolds are successfully fabricated as a promising scaffold of choice for bone tissue engineering and could be used as a potential biomimetic bioactive material for oral and cranio-maxillofacial bone defect repair.