Poly-ε-caprolactone Coated and Functionalized Porous Titanium and Magnesium Implants for Enhancing Angiogenesis in Critically Sized Bone Defects

Abstract

For healing of critically sized bone defects, biocompatible and angiogenesis supporting implants are favorable. Murine osteoblasts showed equal proliferation behavior on the polymers poly-ε-caprolactone (PCL) and poly-(3-hydroxybutyrate)/poly-(4-hydroxybutyrate) (P(3HB)/P(4HB)). As vitality was significantly better for PCL, it was chosen as a suitable coating material for further experiments. Titanium implants with 600 µm pore size were evaluated and found to be a good implant material for bone, as primary osteoblasts showed a vitality and proliferation onto the implants comparable to well bottom (WB). Pure porous titanium implants and PCL coated porous titanium implants were compared using Live Cell Imaging (LCI) with Green fluorescent protein (GFP)-osteoblasts. Cell count and cell covered area did not differ between the implants after seven days. To improve ingrowth of blood vessels into porous implants, proangiogenic factors like Vascular Endothelial Growth Factor (VEGF) and High Mobility Group Box 1 (HMGB1) were incorporated into PCL coated, porous titanium and magnesium implants. An angiogenesis assay was performed to establish an in vitro method for evaluating the impact of metallic implants on angiogenesis to reduce and refine animal experiments in future. Incorporated concentrations of proangiogenic factors were probably too low, as they did not lead to any effect. Magnesium implants did not yield evaluable results, as they led to pH increase and subsequent cell death.

Resorbable bone fixation alloys, forming, and post-fabrication treatments

“…During the process, the oxygen content of the inert gas atmosphere was successfully controlled below 10 ppm to eliminate the chance of oxidation due to the high oxygen affinity of Mg and Mg alloys [221]. Roland et al [222] succeeded to create porous Mg samples using SLM with highest possible resolution achieved of 600 µm.…”

The sense behind retroviral anti-sense transcription

“…Nonetheless, several host transcription factors have been shown to play key roles in inducing transcription from the antisense strand of HIV-1, including Specificity Protein-1 (Sp1) [15, 16] Upstream Stimulating Factor (USF) [17], and Nuclear Factor-kappa B (NF-κB) [8, 16]. Mutagenesis of a conserved USF site has been shown to diminish the activity of the HIV-1 antisense promoter in reporter constructs [17].…”

“…This is due to Sp1 recruitment of transcription factor II-D (TFII-D) which promotes the formation of transcription initiation complexes [16]. Since Sp1 binding to both HIV-1 and HTLV-1 antisense LTRs activates expression of their respective antisense proteins, this ubiquitous transcription factor may also have a key role in driving antisense transcription from the TATA-less ERVK 3′ LTR.…”

Clinical, industrial, and research perspectives on powder bed fusion additively manufactured metal implants

“…8), a concept investigated sporadically using non-AM methods [188]. The ability to control pore structure via L-PBF has promoted the production of a considerable range of resorbable scaffolds [189,190]. The effect of porosity on the degradation rate of the Mg alloy WE43 has been demonstrated in depth, with resorption occurring across the entire scaffold and retention of adequate strength and stiffness for 4-weeks in vitro 190].…”

“…calvarial defect model, however the rate of resorption remained sufficiently high that voids were observed between the implant surface and mineralised bone after 84 days [191]. Magnesium alloys have been the most widely used resorbable alloys [192,193], and as a result a wide range have been processed by L-PBF, including pure Mg, WE43, AZ91 and several Mg-Zn alloys [167,189,190,[194][195][196][197][198][199][200]. When produced by conventional means, Mg alloys and particularly pure Mg show low tensile strength, of the order of 30 MPa when cast, requiring heat treatment as a result [192].…”