| Oral defects commonly involve lesions of both soft and underlying hard tissues because of trauma,inflammatory diseases and tumor resection.Untreated or imperfect treatment on oral soft-hard defects will lead to dysfunction and facial deformities,and even exert negative effect on mental health and quality of life.Three-dimensional(3D)cell printing technique provides the advantages of precise spatial distribution and personalization.In this study,3D cell printing was used to establish a soft-hard construct that is composed of alginate/gelatin(AG)/gingival fibroblast cells(GFs)and alginate/gelatin/nano-hydroxyapatite(AGH)/bone marrow-derived mesenchymal stem cells(BMSCs).Physicochemical results showed that nano-hydroxyapatite(nHA)added in the bioink maintained its crystalline phase.In addition,an increase of viscosity,the improvement of compressive modulus(P<0.01),and slow degradation rate(P<0.01)were found after adding nHA.Scanning electron microscopy analysis showed cell stretched and attached well on the surface of the 3D printed construct.At day 7 after printing,the viability of GFs in AG was 94.80%±1.14,while BMSCs viability in AGH was 86.59%±0.75.PCR results indicated that the expression levels of ALP,RUNX-2,and OCN in BMSCs were higher in AGH than AG bioink(P<0.01),After 8-week implantation into the dorsum of 6-8-week-old male BALB/c nude mice,the cellular printed construct displayed a more integrated structure and better healing of subcutaneous tissue compared with the acellular printed construct.In the cranial defect model,the hard region in the cellular printed construct showed satisfying blood supply and new bone formation next to the defect.In conclusion,this 3D cell printed soft-hard construct exhibits favorable biocompatibility and has potential to promote soft and hard tissue regeneration. |