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Preparation of core-shell poly(L-lactic) acid-nanocrystalline apatite hollow microspheres for bone repairing applications.

Significance Statement

The main goal of bone tissue engineering is the development of biocompatible and biodegradable materials and the fabrication of scaffolds with adequate mechanical properties. The role of the three-dimensional porous scaffolds should be to provide artificial extracellular matrices able to support mechanically and structurally cellular activities, such as cell attachment, proliferation, and differentiation, eventually resulting in new bone formation. In addition these scaffolds could also serve as a reservoir of biologically active signaling molecules regulating cell function and triggering healing process. Conventional monolithic scaffolds, typically combined with cells and growth factors, are still far from leading to successful bone reconstruction in a clinical setting, mainly because of the limited control of biodegradation and drug delivery. A simple but effective solution for these problems could be the introduction of microspheres-based scaffolds. They display several advantages in comparison with traditional monolithic ones e.g., (i) improving control over sustained delivery of therapeutic agents, signaling biomolecules and even pluripotent stem cells, (ii) serving as stimulus-sensitive delivery carriers for triggered release, (iii) introducing porosity and/or improve the mechanical properties of bulk scaffolds by acting as porogen or reinforcement agent, (iv) supplying compartmentalized micro-reactors for dedicated biochemical processes, (v) functioning as cell delivery vehicle, and (vi) giving possibility of preparing injectable and/or mouldable formulations to be applied with a minimally invasive modality.

To this end, in this work we have prepared hollow microspheres (ranging from 10 to 50 µm) based on poly(L-Lactic acid) (PLLA) and biomimetic nanosized hydroxyapatite (HA). PLLA has been chosen because polymers based on lactic acids are now in wide use owing to their biodegradability and biocompatibility, but they are not bone-bioactive, whereas HA which is the mineral phase of bone and dentin, has been commonly used as biomaterial for bone regeneration due to its bioactivity, biocompatibility, osteoconductivity and non-inflammatory properties. The microspheres were prepared by solid particle-stabilized emulsion, the so-called Pickering emulsion, in the absence of any molecular surfactant, where nanoparticles are adsorbed to an oil-water interface. The absence of surfactants is very important in the preparation of biomedical materials since usually the surfactants are undesirable substances because of their non-biodegradability and of the possibility to cause allergic reactions and carcinogenicity. The innovative materials developed in this work should be useful for a variety of biomedical applications including drug delivery system, cell carriers and scaffold for orthopedic, maxillofacial and dental regeneration.

Preparation of core-shell poly(L-lactic) acid-nanocrystalline apatite hollow microspheres for bone repairing applications.

Iafisco M, Palazzo B, Ito T, Otsuka M, Senna M, Delgado-Lopez JM, Gomez-Morales J, Tampieri A, Prat M, Rimondini L.

J Mater Sci Mater Med. 2012 Nov;23(11):2659-69.

 

Dipartimento di Scienze della Salute, Università del Piemonte Orientale, Novara, Italy. [email protected].

Abstract

In this paper, hybrid inorganic-organic core-shell hollow microspheres, made of poly(L-lactic acid) (PLLA) and biomimetic nano apatites (HA), were prepared from biodegradable and biocompatible substances, suitable for bone tissue applications. Preparation is started from Pickering emulsification, i.e., solid particle-stabilized emulsions in the absence of any molecular surfactant, where solid particles adsorbed to an oil-water interface. Stable oil-in-water emulsions were produced using biomimetic 20 nm sized HA nanocrystals as particulate emulsifier and a dichloromethane (CH(2)Cl(2)) solution of PLLA as oil phase. Hybrid hollow PLLA microspheres at three different HA nanocrystals surface coverage, ranging from 10 to 50 um, were produced. The resulting materials were completely characterized with spectroscopic, calorimetric and microscopic techniques and the cytocompatibility was established by indirect contact tests with both fibroblasts and osteoblasts and direct contact with these latter. They displayed a high level of cytocompatibility and thus represent promising materials for drug delivery systems, cell carriers and scaffolds for regeneration of bone useful in the treatment of orthopaedic, maxillofacial and dental fields.

 

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