Production of Hollow Bacterial Cellulose Microspheres Using Microfluidics to Form an Injectable Porous Scaffold for Wound Healing.
Bacterial cellulose (BC) is a biocompatible material with high purity and robust mechanical strength used to fabricate desirable scaffolds for 3D cell culture and wound healing. However, the chemical resistance of BC and its insolubility in the majority of solutions make it difficult to manipulate using standard chemical methods. In this study, a microfluidic process is developed to produce hollow BC microspheres with desirable internal structures and morphology. Microfluidics is used to generate a core-shell structured microparticle with an alginate core and agarose shell as a template to encapsulate Gluconacetobacter xylinus for long-term static culture. G. xylinus then secretes BC, which becomes entangled within the shell of the structured hydrogel microparticles and forms BC microspheres. The removal of the hydrogel template via thermal-chemical treatments yields robust BC microspheres exhibiting a hollow morphology. These hollow microspheres spontaneously assemble as functional units to form a novel injectable scaffold. In vitro, a highly porous scaffold is created to enable effective 3D cell culture with a high cell proliferation rate and better depth distribution. In vivo, this injectable scaffold facilitates tissue regeneration, resulting in rapid wound-healing in a Sprague Dawley rat skin model.
Department of Biomedical Engineering, National University of Singapore, 9 Engineering Drive 1, 117575, Singapore.
Jiaqing
J
Yu
Singapore Institute for Neurotechnology, 28 Medical Drive, #05-COR, 117456, Singapore.
Tzu-Rung
TR
Huang
Department of Biomedical Engineering, National University of Singapore, 9 Engineering Drive 1, 117575, Singapore.
Zhen Han
ZH
Lim
Department of Biomedical Engineering, National University of Singapore, 9 Engineering Drive 1, 117575, Singapore.
Rongcong
R
Luo
Division of Bioengineering, School of Chemical and Biomedical Engineering, College of Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459, Singapore.
Rupali Reddy
RR
Pasula
Singapore Institute for Neurotechnology, 28 Medical Drive, #05-COR, 117456, Singapore.|Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County, 35053, Taiwan.
Lun-De
LD
Liao
Division of Bioengineering, School of Chemical and Biomedical Engineering, College of Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459, Singapore.
Sierin
S
Lim
Department of Biomedical Engineering, National University of Singapore, 9 Engineering Drive 1, 117575, Singapore.|Singapore Institute for Neurotechnology, 28 Medical Drive, #05-COR, 117456, Singapore.
Chia-Hung
CH
Chen
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D045744:Cell Line, Tumor; D002482:Cellulose / Q000008:administration & dosage* / Q000737:chemistry*; D041822:Gluconacetobacter xylinus / Q000737:chemistry*; D006801:Humans; D007267:Injections / Q000379:methods; D008297:Male; D044085:Microfluidics / Q000379:methods; D008863:Microspheres; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods; D014945:Wound Healing / Q000187:drug effects*
D002482:Cellulose
3D cell culture; bacterial cellulose; hollow microspheres; injectable scaffold; wound healing