Gradual pore formation in natural origin scaffolds throughout subcutaneous implantation.
This study used a rat subcutaneous implantation model to investigate gradual in situ pore formation in a self-regulating degradable chitosan-based material, which comprises lysozyme incorporated into biomimetic calcium phosphate (CaP) coatings at the surface to control the scaffold degradation and subsequent pore formation. Specifically, the in vivo degradation of the scaffolds, the in situ pore formation, and the tissue response were investigated. Chitosan or chitosan/starch scaffolds were studied with and without a CaP coating in the presence or absence of lysozyme for a total of six experimental groups. Twenty-four scaffolds per group were implanted, and eight scaffolds were retrieved at each of three time points (3, 6, and 12 weeks). Harvested samples were analyzed for weight loss, microcomputed tomography, and histological analysis. All scaffolds showed pronounced weight loss and pore formation as a function of time. The highest weight loss was 29.8% ± 1.5%, obtained at week 12 for CaP chitosan/starch scaffolds with lysozyme incorporated. Moreover, all experimental groups showed a significant increase in porosity after 12 weeks. At all time points no adverse tissue reaction was observed, and as degradation increased, histological analysis showed cellular ingrowth throughout the implants. Using this innovative methodology, the ability to gradually generate pores in situ was clearly demonstrated in vivo.
Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Taipas, Guimarães 4806-909, Portugal.
Ana M
AM
Martins
James D
JD
Kretlow
Ana R
AR
Costa-Pinto
Patrícia B
PB
Malafaya
Emanuel M
EM
Fernandes
Nuno M
NM
Neves
Catarina M
CM
Alves
Antonios G
AG
Mikos
F Kurtis
FK
Kasper
Rui L
RL
Reis
D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry / Q000378:metabolism; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020007:Implants, Experimental; D008297:Male; D008422:Materials Testing; D009113:Muramidase / Q000378:metabolism; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography
D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D048271:Chitosan; D009113:Muramidase