Development of an Injectable Calcium Phosphate/Hyaluronic Acid Microparticles System for Platelet Lysate Sustained Delivery Aiming Bone Regeneration

• Published in: Macromolecular bioscience 2016-11, Vol.16 (11), p.1662-1677
• Main Authors: Babo, Pedro S., Santo, Vítor E., Gomes, Manuela E., Reis, Rui L.
• Format: Article
• Language: English
• Subjects: Adipocytes - cytology; Adipocytes - metabolism; Antigens, Differentiation - biosynthesis; Blood Platelets - chemistry; Bone Cements - chemistry; Bone Cements - pharmacology; bone regeneration; Bone Regeneration - drug effects; Calcium; Calcium phosphates; Calcium Phosphates - chemistry; Calcium Phosphates - pharmacology; drug delivery; Drug Delivery Systems - methods; growth factors; Humans; Hyaluronic Acid - chemistry; Hyaluronic Acid - pharmacology; injectable CaP cements; platelet lysate; Stem Cells - cytology; Stem Cells - metabolism
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201600141

Despite the biocompatibility and osteoinductive properties of calcium phosphate (CaP) cements their low biodegradability hampers full bone regeneration. Herein the incorporation of CaP cement with hyaluronic acid (HAc) microparticles loaded with platelet lysate (PL) to improve the degradability and biological performance of the cements is proposed. Cement formulations incorporating increasing weight ratios of either empty HAc microparticles or microparticles loaded with PL (10 and 20 wt%) are developed as well as cements directly incorporating PL. The direct incorporation of PL improves the mechanical properties of the plain cement, reaching values similar to native bone. Morphological analysis shows homogeneous particle distribution and high interconnectivity between the HAc microparticles. The cements incorporating PL (with or without the HAc microparticles) present a sustained release of PL proteins for up to 8 d. The sustained release of PL modulates the expression of osteogenic markers in seeded human adipose tissue derived stem cells, thus suggesting the stimulatory role of this hybrid system toward osteogenic commitment and bone regeneration applications. The development of highly degradable injectable calcium phosphate composites for the delivery of platelet‐origin growth factors is reported. The cement composites incorporating platelet lysate are able to release platelet origin growth factors in a controlled manner, and modulate the ratio at which each growth factor was released. Furthermore, the cement composites induce the activation of the osteogenic differentiation pathway.