Bone repair by cell-seeded 3D-bioplotted composite scaffolds made of collagen treated tricalciumphosphate or tricalciumphosphate-chitosan-collagen hydrogel or PLGA in ovine critical-sized calvarial defects.
The aim of this study was to investigate the osteogenic effect of three different cell-seeded 3D-bioplotted scaffolds in a ovine calvarial critical-size defect model. The choice of scaffold-materials was based on their applicability for 3D-bioplotting and respective possibility to produce tailor-made scaffolds for the use in cranio-facial surgery for the replacement of complex shaped boneparts. Scaffold raw-materials are known to be osteoinductive when being cell-seeded [poly(L-lactide-co-glycolide) (PLGA)] or having components with osteoinductive properties as tricalciumphosphate (TCP) or collagen (Col) or chitosan. The scaffold-materials PLGA, TCP/Col, and HYDR (TCP/Col/chitosan) were cell-seeded with osteoblast-like cells whether gained from bone (OLB) or from periost (OLP). In a prospective and randomized design nine sheep underwent osteotomy to create four critical-sized calvarial defects. Three animals each were assigned to the HYDR-, the TCP/Col-, or the PLGA-group. In each animal, one defect was treated with a cell-free, an OLB- or OLP-seeded group-specific scaffold, respectively. The fourth defect remained untreated as control (UD). Fourteen weeks later, animals were euthanized for histo-morphometrical analysis of the defect healing. OLB- and OLP-seeded HYDR and OLB-seeded TCP/Col scaffolds significantly increased the amount of newly formed bone (NFB) at the defect bottom and OLP-seeded HYDR also within the scaffold area, whereas PLGA-scaffolds showed lower rates. The relative density of NFB was markedly higher in the HYDR/OLB group compared to the corresponding PLGA group. TCP/Col had good stiffness to prepare complex structures by bioplotting but HYDR and PLGA were very soft. HYDR showed appropriate biodegradation, TCP/Col and PLGA seemed to be nearly undegraded after 14 weeks. 3D-bioplotted, cell-seeded HYDR and TCP/Col scaffolds increased the amount of NFB within ovine critical-size calvarial defects, but stiffness, respectively, biodegradation of materials is not appropriate for the application in cranio-facial surgery and have to be improved further by modifications of the manufacturing process or their material composition.
Department of Rheumatology, Tissue Engineering Laboratory, Charité-University Medical Center Berlin, Berlin, Germany. j_k.haberstroh@t-online.de
Kathrin
K
Haberstroh
Kathrin
K
Ritter
Jens
J
Kuschnierz
Kai-Hendrik
KH
Bormann
Christian
C
Kaps
Carlos
C
Carvalho
Rolf
R
Mülhaupt
Michael
M
Sittinger
Nils-Claudius
NC
Gellrich
D020341:Absorbable Implants; D000818:Animals; D001861:Bone Regeneration; D002130:Calcium Phosphates; D048271:Chitosan; D003094:Collagen; D004195:Disease Models, Animal; D005260:Female; D006016:Glycolates; D020100:Hydrogels; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012756:Sheep; D012886:Skull / Q000293:injuries* / Q000473:pathology; D013997:Time Factors; D054457:Tissue Scaffolds
D002130:Calcium Phosphates; D006016:Glycolates; D020100:Hydrogels; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen; D048271:Chitosan; C018392:tricalcium phosphate