Novel osteogenic growth peptide C-terminal pentapeptide grafted poly(d,l-lactic acid) improves the proliferation and differentiation of osteoblasts: The potential bone regenerative biomaterial.

Poly(d,l-lactic acid) (PDLLA) is widely used for bone regenerative engineering, because of its proven biocompatibility and biodegradability. However, the major limitation of PDLLA is its cell recognition and low hydrophilicity. The objective of this study was to develop a novel bioactive poly(d,l-lactic acid) tethered with osteogenic growth peptide (OGP), which has been confirmed as one of the important growth factors related to bone repair/regeneration. The biomimetic material modification methods were utilized that maleic anhydride-modified poly(d,l-lactic acid) (MPLA) as raw material, the active C-terminal pentapeptide OGP(10-14) were covalently grafted onto the side chain of MPLA through amide reaction using 1­ethyl­3­(3­dimethyl aminopropyl) carbodiimide hydrochloride (EDC) and N­hydroxysuccinimide (NHS) as the condensing agent to produce a new biopolymer (OGP(10-14)-MPLA). The OGP(10-14)-MPLA were further characterized with the Fourier transform infrared spectrometry, amino acid analyzer, elementary analysis, X-ray photoelectron spectroscopy. The results revealed that OGP(10-14) was successfully modified MPLA and its coupling efficiency was 12.40%. The data from both contact angle and water absorption showed the better hydrophilicity of OGP(10-14)-MPLA, compared with MPLA. Also, we found that OGP(10-14)-MPLA could improve the proliferation, differentiation, and mineralization of osteoblasts, indicating that the novel OGP(10-14)-MPLA has the better biocompatibility and is more osteoinductive. In conclusion, the OGP(10-14) modified MPLA have the potential for bone regenerative engineering.

Mechanically induced autophagy is associated with ATP metabolism and cellular viability in osteocytes in vitro.

Both mechanical loading and intracellular autophagy play important roles in bone homeostasis; however, their relationship remains largely unexplored. The objectives of this study were to determine whether osteocytes undergo autophagy upon fluid shear stress (FSS) loading and to determine the correlation between mechanically induced autophagy and ATP metabolism. Autophagic vacuoles were observed by transmission electron microscopy (TEM) in osteocyte-like MLO-Y4 cells subjected to FSS. Increased autophagic flux was further confirmed by the increased amount of the LC3-II isoform and the degradation of p62. Fluorescent puncta distributed in the cytoplasm were observed in the GFP-LC3 transformed cells subjected to FSS. Furthermore, FSS-induced ATP release and synthesis in osteocytes were attenuated by inhibiting autophagy with 3-MA. After FSS exposure, a high ratio of cell death was observed in cultures pretreated with 3-MA, an autophagy inhibitor, with no significantly different Caspase 3/7 activity. Our results indicated that FSS induces protective autophagy in osteocytes and that mechanically induced autophagy is associated with ATP metabolism and osteocyte survival. From the clinical perspective, it may be possible to enhance skeletal cell survival with drugs that modulate the autophagic state, and the autophagy-related pathway could be a potential target for the prevention of ageing-related bone disorders.