Engineering bone regeneration with novel cell-laden hydrogel microfiber-injectable calcium phosphate scaffold

Abstract

Cell-based tissue engineering is promising to create living functional tissues for bone regeneration. The implanted cells should be evenly distributed in the scaffold, be fast-released to the defect and maintain high viability in order to actively participate in the regenerative process. Herein, we report an injectable calcium phosphate cement (CPC) scaffold containing cell-encapsulating hydrogel microfibers with desirable degradability that could deliver cells in a timely manner and maintain cell viability. Microfibers were synthesized using partially-oxidized alginate with various concentrations (0-0.8%) of fibrinogen to optimize the degradation rate of the alginate-fibrin microfibers (Alg-Fb MF). A fibrin concentration of 0.4% in Alg-Fb MF resulted in the greatest enhancement of cell migration, release and proliferation. Interestingly, a significant amount of cell-cell contact along the long-axis of the microfibers was established in Alg-0.4%Fb MF as early as day 2. The injectable tissue engineered construct for bone reconstruct was fabricated by mixing the fast-degradable Alg-0.4%Fb MF with CPC paste at 1:1 volume ratio. In vitro study showed that cells re-collected from the construct maintained good viability and osteogenic potentials. In vivo study demonstrated that the hBMSC-encapsulated CPC-MF tissue engineered construct displayed a robust capacity for bone regeneration. At 12weeks after implantation, osseous bridge in the rat mandibular defect was observed in CPC-MF-hBMSCs group with a new bone area fraction of (42.1±7.8) % in the defects, which was >3-fold that of the control group. The novel tissue-engineered construct presents an excellent prospect for a wide range of dental, craniofacial and orthopedic applications.

Calcium phosphate cements for bone engineering and their biological properties

“…At 12 weeks, an osseous bridge in the rat mandibular defect was observed in the CPC-microfiber-hBMSCs group with a new bone area fraction of 42.1%±7.8%, which was threefold greater than that of the control group ( Figure 5 ). 139 Therefore, these results demonstrate that injectable hydrogel microfiber-CPC paste is a promising carrier for cell delivery and greatly enhances bone regeneration in vivo .…”

Tissue engineering applications in otolaryngology—The state of translation

“…Furthermore, the study of growth signaling has become important for growth of alveolar, maxillary, and mandibular TE constructs. A plethora of graft biomaterials and biochemical factors have been studied with the goal of improving the tissue‐engineered construct's scaffold integration and tissue growth 48‐58,66‐79 …”

“…Heatmap representing the proportion of publications by year that utilized specific translational research methodologies from construct characterization to human trial to investigate craniofacial tissue engineering 49‐72,74‐77,79,81‐84,145‐197 …”

Periodontal Bone-Ligament-Cementum Regeneration via Scaffolds and Stem Cells

“…Therefore, a resorbable and injectable alginate-microfibers/microbeads (Alg-MB/MF) delivery system for stem cells was developed, which protected the encapsulated stem cells during the CPC paste blending and injection [39]. It supported cell health, proliferation and differentiation, with microbeads degrading at 3–4 days and releasing the encapsulated cells (Figure 1d–o) [40,41]. In a recent study [42], six types of stem cells: human bone mesenchymal stem cells (hBMSCs), human dental pulp stem cells (hDPSCs) [43,44], human umbilical cord MSCs (hUCMSCs), MSCs derived from embryonic stem cells (hESC-MSCs), human induced pluripotent stem cell-MSCs derived from bone marrow (BM-hiPSC-MSCs) and from foreskin (FS-hiPSC-MSCs), were encapsulated in hydrogel microfibers and microbeads inside an injectable CPC.…”