Table 5.

In vitro and in vivo experiments are classified according to the material and the strategy adopted with the aims of enhancing the scaffolds performances. In the first row the main strategies used to make the polymers suitable for bone scaffolds are reported. In the second row, the fundamental common aim for each strategy. All the analyzed studies in this review have been here classified according to both the material and the strategy adopted. In addition to the achieved general aim, the relevant evidences specific for each combination of material and strategy have been resumed in the table. Almost half of the reported studies overcame the polymers main limit of low mechanical feature by addition of inorganic materials (second column). This strategy not only guanteed an increased mechanical strenght but also favored the cells activities, as specifically reported for each material-strategy combination. In the third column, the several studies involving chemical factors/drugs addition to enhance the polymers osteoactivies. In the fourth column are reported the references where polymers - mainly the natural ones - are used as minor component to enhance the bioactivity or as reinforcement (only in silk and cellulose cases) of other bulk materials. Just few studies can not be included according to the described criteria and are reported in the firth column. The residual number of the studies in the “other stretegies” column confirmed the reported strategies as the most applied ones to obtain the ideal scaffold, that aim to both overcome the polymers limits and enchance their characteristics. The hydrogel/injectable matierals are indicated with ¹.

Strategy	Inorganic Material Addition	Chemical Factor/Drug Addition	As Minor Component	Other Strategies
Main Aim	To increase the mechanical properties	To enhance osteoactivities	To increase cytocompatibility of other materials
Collagen	Facilitate pore interconnectivity good porosity, cell infiltration, cell differentiation, angiogenesis and osteogenesis [69,70,71,72,73,74]	Appropriate scaffold porosity, swelling, and drug release [75,76]1 [90,91,104]	Increased osteogenesis, and osteoblast differentiation [68]	[66,67][75]1
Gelatin	Relevant osteoconductive properties [80,81,89] [79,103,122] 1	New bone formation [78,80][122] 1		[77]
Silk fibroin	Good stem cells differentiation, cells attachment, and osteogenesis [84,85,88][86] 1	Increased osteogenic potential [83]	Increased compressive strenght of bone cement; increased prolifertion and osteogenic differantiation [87,88]	[82]
Chitosan	Good osteogenic cell differentiation [89,92,94][93] 1	Suitable drug release and enhanced osteogenic differentiation [90,91,92] [75,93]1 [94,99,109]	[98] 1
Alginate	Osteodifferentiation, increased cell adhesion and osteogenesis [95] 1 [94,96,97]	Good results in cell viability, osteogenic differentiationand cell adhesion and controlled drugs release [94,95,99]	Increased osteogenesis in bone cement [98]1	[100,101,102]1
Cellulose	Increased osteoblast proliferation, differentiation, and osteoconductivity [118,119,121][120,122]1	Controlled drug release, osteoblastic differantiation, and new bone formation [122]1 [117,124]	Increased compressive strenght and in vitro stability; improved cell attachement, viability, proliferation, and calcium deposition [115,116,117,123]	[111,112,114] [113] 1
Hyaluronic acid	Good porosity, proliferation and mineralization [103,105] 1	High cell adhesion, proliferaration and migration, vibility, and calcium deposition [104][105,105,106,107,108,109] 1		[102]
PCL	Increased cell attachment, proliferation, differentiation, calcium deposition, and bone formation [128,129,130,131,132]	Increased cellular attachment, angiogenesys, and osteogenesis [130,131]		[126,127]
PLA	Good cell adhesion proliferation, and osteo-differentiation [134,136]	Rapid and complete drug release, good cell viability, proliferation, and osteogenic differentiation [136]		[133,135]
PLGA	Good porosity, osteogenic potential, and mineralization activity, higher cellular adhesion/proliferatio, and new bone formation [137,138,139,140,141,142,144,145][143] 1	Higher initial adhesion, increased proliferation, new bone formation, and suitable scaffold integration; controlled drug release. [144,147,148]	Good cell viability, proliferation, and osteogenic differentiation [145]	[146]

¹ Hydrogel/ Injectable material.