Modular Orthopaedic Tissue Engineering With Implantable Microcarriers and Canine Adipose-Derived Mesenchymal Stromal Cells

Abstract

Mesenchymal stromal cells (MSC) hold significant potential for tissue engineering applications. Modular tissue engineering involves the use of cellularized “building blocks” that can be assembled via a bottom-up approach into larger tissue-like constructs. This approach emulates more closely the complexity associated hierarchical tissues compared with conventional top-down tissue engineering strategies. The current study describes the combination of biodegradable porous poly(DL-lactide-co-glycolide) (PLGA) TIPS microcarriers with canine adipose-derived MSC (cAdMSC) for use as implantable conformable building blocks in modular tissue engineering applications. Optimal conditions were identified for the attachment and proliferation of cAdMSC on the surface of the microcarriers. Culture of the cellularized microcarriers for 21 days in transwell insert plates under conditions used to induce either chondrogenic or osteogenic differentiation resulted in self-assembly of solid 3D tissue constructs. The tissue constructs exhibited phenotypic characteristics indicative of successful osteogenic or chondrogenic differentiation, as well as viscoelastic mechanical properties. This strategy paves the way to create in situ tissue engineered constructs via modular tissue engineering for therapeutic applications.

Biodegradable Microparticles for Regenerative Medicine: A State of the Art and Trends to Clinical Application

“…Aggregation of the biodegradable microparticles leading to the formation of larger objects could be realized using either chemical/physical interactions of microparticle surfaces or via interactions through cells seeded onto the microparticles [ 106 ]. The second approach is more interesting and consists of two stages, when (1) the microparticles used for cell expansion have their surface covered by cells, and (2) cell culture continues at milder conditions to promote cell-cell interactions [ 107 ]. This strategy of microparticle application needs significant control over MPs surface characteristics [ 108 ] and culture conditions [ 107 ].…”

“…The second approach is more interesting and consists of two stages, when (1) the microparticles used for cell expansion have their surface covered by cells, and (2) cell culture continues at milder conditions to promote cell-cell interactions [ 107 ]. This strategy of microparticle application needs significant control over MPs surface characteristics [ 108 ] and culture conditions [ 107 ]. Aggregation of the cell-laden microparticles could be carried out in vitro with an aim to form complex tissue/organ for further implantation, or cell-seeded microparticles could be firstly injected into the targeted tissue and agglomerate in situ by the action of the cells [ 109 ].…”

“…An additional advantage offered by this strategy will be that these microparticles will multiply the surface requested to support cell proliferation and differentiation. In terms of perspectives of valorization, this strategy also seems very attractive, taking into account the following aspects: Their local administration is minimally invasive and feasible into limited accessible sites; Their high surface/volume ratio is favorable and reported to be particularly suited as cell supporting microcarriers; Being made from well-known biocompatible and biodegradable polyesters, such as PLGA; Their degradation rate can be easily adjusted to balance growth factor release kinetics, cell supporting amplification, and mechanical support [ 107 ]; The large scale GMP production of these drug delivery microparticles is already known and applied for several years; They are simple products, free of animal cells, and easy to submit to regulatory bodies; There is an opportunity to physically combine these microparticles with autologous stem cells just before implantation on a patient. …”

“…Their degradation rate can be easily adjusted to balance growth factor release kinetics, cell supporting amplification, and mechanical support [ 107 ];…”

Manufacturing, characterization, and degradation of a poly(lactic acid) warp-knitted spacer fabric scaffold as a candidate for tissue engineering applications

“…Biomaterials Science size, with fixed overall porosity and pore size Moreover, the of Entezari et al, 67 who demonstrated possibility of using weak biomaterials in modular scaffolds for repairing large bone defects, with only few percent of strain being sufficient to promote osteogenesis, supports our proposed use of the present scaffold for the repair of non and load-bearing tissues. The bioabsorbable scaffold developed here can also be used in bottom-up tissue engineering strategies, 54,68 culturing different cell types on different fabric layers, which assembled could better mimic the native tissue environment and improve tissue healing. Even though some scaffold requirements are specific to each tissue and a single scaffold design is unlikely to meet the requirements of all human tissues; we propose bioabsorbable warp-knitted spacer fabrics as versatile platform for scaffold manufacturing.…”