Table 1. Survey of the in vitro and in vivo studies about embroidered and surface modified PCL scaffolds as bioartificial bone substitute.

Study	Study design	Methods	Main results	Reference
In vitro studies	Material: non-coated, NaOH treated, Coll I and Coll I/CS coated PCL scaffolds Scaffold design: round, 1 mm thick, 14 mm outer and 4 mm inner diameter or 19 mm outer and 10 mm inner diameter Cells: MSC Analysis: - Scaffold properties (structure, porosity, pore size), - Adherence, proliferation and differentiation of MSC	- Micro computered tomography, - Scanning electron microscopy, - Contact angle measurement, - Quantification of CS and Coll I (toluidine blue and sirius red), - Measurement of lactate dehydrogenase and alkaline phosphatase, - Calcium measurement (o-cresolphthalein complexone) and histology (von Kossa), - Reverse transcriptase polymerase chain reaction (alkaline phosphatase, bone sialoprotein)	- Adequate porosity and pore size - Coll I enhanced cell attachment and proliferation - Coll I/CS induced osteogenic differentiation of MSC without differentiation additives	7, 8, 9
In vivo study, orthotopic (femur), immunodeficient nude rat	Material/groups: non-coated, Coll I and Coll I/CS coated and Coll I/CS coated/hMSC seeded PCL scaffolds, 5 animals per group Scaffold design: round, 0.5 mm thick, 5 mm diameter, stack of 10 scaffolds per defect Cells: hMSC undifferentiated Animal model: 5 mm critical size defect, duration12 weeks	- Radiography, computered tomography and final bone volume quantification - Histology/immunohistology: estimation of new bone formation (trichrome masson-goldner, osteopontin, osteonectin, collagen II), quantification of vessel formation (smooth muscle actin), cells survival (human nuclei), quantification of matrix deposition (histomorphometry)	- Coll I coating acts as matrix for cell adhesion and proliferation - Coll I/CS coating allowed recruiting of cells, osteogenic stimulation and induction of new bone formation - Additional cell seeding showed higher matrix accumulation and vascularization, but could not clearly improve new bone formation	10
Pilot in vivo study, orthotopic (tibia), sheep	Material/groups: Coll I/CS coated PCL, scaffolds, 5 animals per group and time point Scaffold design: 1 mm thick, 19 mm outer, 10 mm inner diameter, stack of 30 scaffolds Animal model: 3 cm critical size defect, duration12 and 48 weeks	- Radiography, computered tomography, micro computered tomography, - Bone volume quantification - Histology (trichrome masson-goldner), - Biomechanics	- Appropriate network of pores to permit a complete vascularization and bone tissue formation - New bone formation at the proximal and distal tibia fragments increasing over time - Bridging the defect up to defect healing in 50 % of the animals

Polycaprolactone-co-lactide (trade name: PCL, Catgut GmbH), Collagen I (Coll I), chondroitin sulfate A (CS), mesenchymal stem cells (hMSC).