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International Journal of Bioprinting                                Immunomodulatory bone repair by MBG/PCL




            and that this group was the most capable of mediating macrophage polarization and thus inducing the osteogenic
            differentiation of rat bone marrow mesenchymal stem cells (BMSCs) to form an immune microenvironment conducive
            to osteogenesis. This study is a step forward in the exploration of the performance of BG composite PCL scaffolds and
            provides a new idea for the development of bone graft materials.


            Keywords: 3D printing; Dendritic mesoporous structured bioactive glass; Macrophages; Bone marrow mesenchymal
            stem cells; Immunoregulation; Osteogenic differentiation



            1. Introduction                                    material, resulting in composites with excellent bone
                                                               and vascular regeneration properties. 13,14  For example,
            Currently, bone  defects  due  to  factors  such  as  trauma   Zhao et al. used mesoporous BGs composite fiber protein
            or surgery are becoming more and more common.      hydrogel for maxillofacial bone defects.  The results
                                                                                                  15
            According to statistics, millions of patients  with bone   showed the enhancement effect of mesoporous BGs on
            defects worldwide require autologous bone grafting
            every year, but the inadequate sources and donor sites of   the mechanical strength, bioactivity, and osteogenesis
                                                               of the material. As mentioned above, BGs improve the
            autologous bone limit its application.  The development   hydrophilic properties of PCL and enhance its osteogenic
                                          1-3
            of bone tissue engineering has promoted the emergence   activity, while PCL as an engineered scaffold matrix can
            of engineered scaffolds on the market. Good mechanical
            properties, biocompatibility, and osteogenic activity are   provide a stable support medium for bone defect repair.
            the basic requirements for engineered scaffolds used in   However, the dense pores and low specific surface area of
            bone graft substitution.  Polycaprolactone (PCL) is one of   ordinary BGs and mesoporous BGs limit the mechanical
                               4
            the commonly used materials for bone tissue engineering   properties and bioactivity of the overall scaffold. Therefore,
            because of its high biocompatibility. However, PCL is   the  current composite scaffolds  show a  continuous
            hydrophobic and lacks osteogenic potential, and is often   increase in compressive strength and osteogenic activity
            used as a matrix component of composite scaffolds in bone   with increasing glass content. For instance, Wang et al.’s
            tissue engineering. 5,6                            study on the osteogenic properties of BGs/PCL scaffolds
                                                               showed that scaffolds with the highest BGs percentage
               Since the invention of bioglass 45S5 by Prof. Larry   (20%) possessed the highest mechanical strength and
            Hench in the 1970s, the field of medical materials has   osteogenic activity.  But this seems to be detrimental to
                                                                              16
            opened up to the study of coordinated osteointegration   the degradation and resorption of BGs in vivo.
            of bioglasses.  Bioglass 45S5 accelerates bone formation
                       7
            by releasing Na  and rapidly exchanging it with H     More  importantly,  bone  regeneration  and  repair
                                                          +
                          +
                                                                                                            17
            and HO  to form a silica layer on the silica-based   are closely related to the immune microenvironment.
                    +
                   3
            surface, and then by recruiting ions such as Ca  and   “Osteoimmunology,” first proposed by Joseph R. Arron
                                                     2+
            P  to form a hydroxycarbonate apatite layer (HCA).     and Yongwon Choi, focuses on revealing the interplay
             5+
                                                         7-9
                                                                                                            18
            Nevertheless, high-temperature sintered bioglass is   between bone cell remodeling and immune cells.
            prone to agglomeration and has low specific surface area,   Studies have shown that the immune microenvironment
            which affects its biological activity. In addition, the Na    influences bone regeneration, with macrophages (MPs)
                                                          +
                                                                                               19
            and Ca  ions released from the degradation of bioglass   playing a central role in osteogenesis.  However, MPs
                  2+
            may cause cytotoxicity due to the change of local pH   exhibit plasticity and can polarize toward either M1
            and delay the formation of HCA.  These drawbacks   or M2 phenotypes. The pro-inflammatory phenotype
                                          10
            limit the application of bioglass 45S5. Fortunately, due   M1 induces tissue inflammatory responses, while the
                                                                                                  20
            to the use of templating agents (CTAC, P123, F127),   M2 phenotype is involved in tissue repair.  As a result,
            bioactive glasses (BGs) with mesoporous structures   the ability of biomaterials to immunomodulate MPs
            have emerged in  the research landscape.  Mesoporous   polarization from M1 to M2 is one of the keys to bone
                                                                          17
            BGs have better histocompatibility, their ordered   regeneration.  It has been demonstrated that BGs can
            mesoporous structure increases their bioactivity, and   modulate the host immune response to the implant
            ions such as Si , Ca , and P  released during  in vivo   and promote MPs polarization to the M2 phenotype,
                             2+
                        2+
                                     5+
            degradation contribute to the formation of the bone   creating an immune microenvironment favorable for
            matrix such as hydroxyapatite. 11,12  Studies have shown   stem cell differentiation. 21-23  This may be because the
            that the incorporation of mesoporous BGs can enhance   ionic products such as Si  and Ca  degraded by BGs
                                                                                    2+
                                                                                             2+
            the mechanical properties and bioactivity of the matrix   modified the original ionic microenvironment. 24,25
            Volume 10 Issue 5 (2024)                       321                                doi: 10.36922/ijb.3551
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