## 4 Enhanced Barrier Membranes
### Membranes with Inorganic Compounds  
In order to enhance the osteoconductive and osteoinductive effects, research has focused on the introduction into the structure of the barrier membrane of synthetic calcium phosphates (hydroxapatite or \(\beta\)-tricalcium phosphate), single or combined in biphasic calcium phosphates. Such products allow vascular penetration, cell infiltration and attachment, cartilage formation and calcified tissue deposition [94; 95]. [PERSON] et al. [95] showed that the membrane made of a mixture of particles of PCL, collagen and hydroxyapatite generated a rapid cell spread and a significant cell proliferation. [PERSON] et al. [96] evaluated the effects of collagen membrane and a membrane of chitosan, fibroin and hydroxyapatite on calvarial defect in rats; the results were similar for both types of membranes, with the absence of inflammatory reactions [96].  
[PERSON] et al. [97] compared the collagen membrane with a membrane made of PCL, PLGA and \(\beta\)-tricalcium phosphate; even if both membranes showed similar results in histological and histomorphometric analyses, the membrane made of PCL, PLGA and \(\beta\)-tricalcium phosphate generated a larger area of bone neo-formation [97].  
Other studies have looked into potential effects of including zinc, magnesium, iron or strontium in the composition of the membrane. Zinc is an absolutely necessary mineral for skeletal growth and development [98], important in many physiological and metabolic processes [99]. The addition of ZnO in the structure of barrier membranes has generated improvements in the proliferation of osteoblasts, with an accelerated regenerative mechanism [100]; the use of zinc membranes has also demonstrated a faster healing process [101], as well as inhibiting the formation of bacterial biofilm [102; 103]. In addition, [PERSON] et al. [104] observed that PLA-Zn-bioactive glass membranes showed tensile strength, elongation and flexibility similar to those of zinc-free membranes [104].  
Similar to zinc, magnesium is an important factor in bone metabolism, with both proliferative effects for osteoblasts and anti-osteoclastic effects [105]. The strength of the Mg alloy is higher than that of absorbable polymers, such as PLA; therefore, magnesium alloy can improve the mechanical properties of membranes. However, the rate of the degradation of magnesium alloy is too fast [106]. An in vitro study found that hydrofluoric acid coating can delay the corrosion of magnesium alloys [107]. [PERSON] et al. [108] designed a barrier membrane made of PLA reinforced with a Mg alloy core, with a better loading capacity compared to membranes without Mg reinforcement; when fluorine-coated magnesium alloy was used, it showed better resistance to corrosion. The proliferation of fibroblasts and osteoblasts has also been easily achieved [109].  
Strontium is involved in bone mineral metabolism by inducing osteogenesis, stimulating markers of differentiation and proliferation, and reducing apoptosis levels [109]. [PERSON] et al. [110] studied the effect of covering rabbit calvarial defects with a collagen membrane with strontium and hydroxyapatite; after 24 weeks, they observed increased levels of newly mineralized bone and less residual grafting material compared to an unmodified collagen membrane [110].  
Thus, membranes enhanced with inorganic compounds could offer a favorable alternative in GTR and GBR, but additional data are needed to optimize the protocols for the use of these membranes.