3D and Porous RGDC‐Functionalized Polyester‐Based Scaffolds as a Niche to Induce Osteogenic Differentiation of Human Bone Marrow Stem Cells

Abstract

Polyester‐based scaffolds covalently functionalized with arginine‐glycine‐aspartic acid‐cysteine (RGDC) peptide sequences support the proliferation and osteogenic differentiation of stem cells. The aim is to create an optimized 3D niche to sustain human bone marrow stem cell (hBMSC) viability and osteogenic commitment, without reliance on differentiation media. Scaffolds consisting of poly(lactide‐co‐trimethylene carbonate), poly(LA‐co‐TMC), and functionalized poly(lactide) copolymers with pendant thiol groups are prepared by salt‐leaching technique. The availability of functional groups on scaffold surfaces allows for an easy and straightforward method to covalently attach RGDC peptide motifs without affecting the polymerization degree. The strategy enables the chemical binding of bioactive motifs on the surfaces of 3D scaffolds and avoids conventional methods that require harsh conditions. Gene and protein levels and mineral deposition indicate the osteogenic commitment of hBMSC cultured on the RGDC functionalized surfaces. The osteogenic commitment of hBMSC is enhanced on functionalized surfaces compared with nonfunctionalized surfaces and without supplementing media with osteogenic factors. Poly(LA‐co‐TMC) scaffolds have potential as scaffolds for osteoblast culture and bone grafts. Furthermore, these results contribute to the development of biomimetic materials and allow a deeper comprehension of the importance of RGD peptides on stem cell transition toward osteoblastic lineage.

Comparison of Scaffolds Fabricated via 3D Printing and Salt Leaching: In Vivo Imaging, Biodegradation, and Inflammation

“…The implantation of scaffold can change the host response as a foreign body reaction [ 28 , 29 ]. It has been proposed that mechanical properties of the interface between a scaffold and its surrounding tissues are critical for determining the host response; however, the underlying inflammatory mechanism is still poorly understood.…”

“…The printed PCLA scaffolds contained slightly more ED1-positive cells than the salt-leached PCLA scaffolds. We surmised that the printed PCLA scaffolds as foreign bodies induced a slightly stronger inflammation reaction because they remained in the body longer [ 28 , 29 ].…”

A review of biomimetic scaffolds for bone regeneration: Toward a cell‐free strategy

“…The RGD motif is a cell-recognizable sequence discovered [188] regularly distributed along the polymeric chains, a niche with the ability to promote the interaction between scaffold materials and cells can be constructed. Results indicated that the use of the RGDC-functionalized scaffolds produced increased ALP activity and upregulated osteocalcin expressed compared to controls [193]. Furthermore, a cell-free and growth factor-free hydrogel that can induce angiogenesis ， osteogenesis, and innervation has been created.…”

“…Sr/BG-G/nHAp Freeze-drying Oryan et al [7] SrHAp/CS Lei et al [39] Sr/MgP bioceramics Solid state sintering Sarkar et al [9] Zn-MBGNs Microemulsion-asisted sol-gel Neščáková et al [10] dECM/BCP Freeze-thaw /SDS solution immersion Kim et al [13] CS/G/A-dECM MOIP-PLGA Thermal-induced phase separation Shen et al [95] HA-MA/PLGA Controlled directional cooling/ lyophilization Dai et al [97] RAFSs Electrospinning Shin et al [98] SiO2 NF-CS Sol-gel electrospinning/ lyophilization Wang et al [111,112] SiO2-CaO NF/CS PLA/PLA-HA 3D printing/casting/salt leaching Grottkau et al [260] BG-CFS Solvothermal method/3D printing Dang et al [116] Ca-P/polydopamine nanolayer surface 3D printing Ma et al [134] MoS2 nanosheets and AKT bioceramic 3D printing/hydrothermal method Wang et al [117] nHA/GO/CS Modified Hummer's method/ lyophilization Ma et al [30] BPs-PLGA Solvent exfoliation/ solvent evaporation Tong et al [118] Hierarchical intrafibrillarly mineralized collagen(HIMC) Two steps self-assembly Liu et al [29] CFO@BFO/PLLA Microfluidic device/hydrothermal / sol-gel Mushtaq et al [150] Fe3O4/MBG/PCL Co-precipitation/3D printing Zhang et al [157] PVDP/CoFe2O4 Solvent casting Fernandes et al [262] nHA/Fe3O4 NPs-CS/COL Crystallization/freeze-drying Zhao et al [263] Ti/W/TiO2 Two-photon lithography(TPL) direct laser writing Maggi et al [27] Porine demineralized bone matrix scaffolds Decalcification Hu et al [175] [193] rGO/BG/osteoblast-specific aptamer Evaporation-induced self-assembly/ heat-treating/reciprocating oscillation Wang et al [203] Van-pBNPs/pep@pSiCaP-Ti Adapted with permission [31]. Fig.9 Schematic illustration of the construction of nHA/GO particles, nHA/GO/CS scaffolds, and their bio-applications.…”

Multipurpose Degradable Physical Adhesive Based on Poly(d,l‐lactide‐co‐trimethylene Carbonate)

“…Biomedical devices manufactured using degradable polymers, such as aliphatic polyesters [ 1 ] and related copolymers also with cyclic carbonates, [ 2,3 ] can help in solving the challenges encountered in tissue regeneration as well as serve as a niche [ 4 ] for in vitro cell studies.…”