REGENERATIVE ENGINEERING

Nanofiber-hydrogel composite for soft tissue remodeling and regenerative therapy

We have developed an injectable nanofiber-hydrogel composite material (US patent issued in 2019) that retains needed structural integrity while maintaining sufficient porosity to enable host cell infiltration and vascularization, and that provides biostimulatory conditioning of the tissue environment without relying on exogenous growth factors (Li, et al, 2019). This composite material combines high porosity of hyaluronic acid hydrogel with tunable stiffness and structural reinforcement feature of the composite by incorporating electrospun poly(ε-caprolactone) (PCL) nanofiber fragments that are covalently conjugated to the HA network. The covalent interfacial bonding in the composite structure enables mechanical properties mimicking those of native soft tissues while retaining an open, porous architecture encouraging host tissue infiltration and remodeling for soft tissue repair (Henn, et al, 2020) and spinal cord regeneration (Li, et al, 2020; Haggerty, et al, 2022).

Representative Publications:

  1. Li X, Cho B, Martin R, Seu M, Zhang C, Zhou Z, Choi JS, Jiang X, Chen L, Walia G, Yan J, Callanan M, Liu H, Colbert K, Morrissette-McAlmon J, Grayson W, Reddy S, Sacks JM, Mao HQ. Nanofiber-hydrogel composite-mediated angiogenesis for soft tissue reconstruction. Sci. Transl. Med. 11(490). pii: eaau6210 (2019). PMID: 31043572.
  2. Li X, Zhang C, Haggerty AE, Yan J, Lan M, Seu M, Yang M, Marlow MM, Maldonado-Lasunción I, Cho B, Zhou Z, Chen L, Martin R, Nitobe Y, Yamane K, You H, Reddy S, Quan DP, Oudega M, Mao HQ. The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord. Biomaterials. 245: 119978 (2020). PMCID: PMC8787820; PMID: 32217415.
  3. Haggerty AE, Maldonado-Lasunción I, Nitobe Y, Yamane K, Marlow MM, You H, Zhang C, Cho B, Li X, Reddy S, Mao HQ, Oudega M. The effects of the combination of mesenchymal stromal cells and nanofiber-hydrogel composite on repair of the contused spinal cord. Cells. 2022 11(7): 1137 (2022). PMCID: PMC8997442; PMID: 35406701.
  4. Henn D, Fischer KS, Chen K, Greco AH, Martin RA, Sivaraj D, Trotsyuk AA, Mao HQ, Reddy SK, Kneser U, Gurtner GC, Schmidt VJ, Sacks JM. Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Regenerative Macrophage Polarization and Vascularization for Soft-Tissue Engineering. Plastic and Reconstructive Surgery. 149(3): 433e-444e. doi: 10.1097/PRS.0000000000008872. PMID: 35196680 (2022)
  5. Yao ZC, Yang YH, Kong J, Zhu Y, Li L, Chang C, Zhang C, Yin J, Chao J, Selaru FM, Reddy SK, Mao HQ. Biostimulatory Micro-Fragmented Nanofiber-Hydrogel Composite Improves Mesenchymal Stem Cell Delivery and Soft Tissue Remodeling. Small. 18(36): e2202309. doi: 10.1002/smll.202202309. Epub 2022 Aug 10. PMID: 35948487 (2022).

Electrospun polymer nanofibers for stem cell culture and regenerative engineering

We have developed electrospun nanofibrous matrix to mimic the biochemical and topographical characteristics of the basement membrane to synergistically improve the self-renewal and proliferation, while maintaining the phenotype of human hematopoietic stem/progenitor cells (HSPCs) (Chua et al, 2006, 2007, Jiang et al, 2011), and demonstrated the potential of nanofiber-expanded cells for angiogenic therapies in treating heart and limb ischemia and osteoporosis. We have developed nanofiber matrix as an extrinsic cue to promote preferential differentiation of stem cells and generate functional progenitors and tissue cells for regenerative therapies, including neural stem cells (Christopherson, et al, 2009; Lim, et al, 2010; Mahairaki, et al, 2011), human embryonic stem cell (ESC)-derived neural crest stem cells (Ren, et al, 2012), and human ESC-derived retinal ganglion cells (Slush et al, 2015). We have developed a patented electrostretching method to generate hydrogel microfiber bundles with embedded nanofiber topography using aqueous solutions of natural polymers (Zhang, et al, 2014), and demonstrated its utility as a 3D scaffold with internal alignment cue to induce organized cell/tissue regeneration: electrospun fibrin fibers for arterial vascular engineering (Barreto-Ortiz, 2013; 2015; Elliot, et al, 2019) and skeletal muscle myofiber regeneration (Gilbert-Honick, et al, 2018, 2020; Somers, et al, 2019; Morrissette-McAlmon, et al, 2020).

Representative Publications:

  1. Chua KN, Chai C, Lee PC, Tang YN, Ramakrishna S, Leong KW, Mao HQ. Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells. Biomaterials. 27(36): 6043–6051 (2006). PMID: 16854459. 
  2. Christopherson GT, Song H, Mao HQ. The influence of fiber diameter of electrospun substrates on neural stem cell differentiation and proliferation. Biomaterials. 30(4): 556–564 (2009). PMID: 18977025. 
  3. Zhang S, Liu X, Barreto-Ortiz SF, Yu Y, Ginn BP, DeSantis NA, Hutton DL, Grayson WL, Cui FZ, Korgel BA, Gerecht S, Mao HQ. Creating polymer hydrogel microfibres with internal alignment via electrical and mechanical stretching. Biomaterials. 35(10): 3243–3251 (2014). PMCID: PMC3923323. PMID: 24439410.
  4. Elliott MB, Ginn B, Fukunishi T, Bedja D, Suresh A, Chen T, Inoue T, Dietz HC, Santhanam L, Mao HQ, Hibino N, Gerecht S. Regenerative and durable small-diameter graft as an arterial conduit. Proceedings of the National Academy of Sciences of the United States of America. 116(26): 12710–12719 (2019). PMCID: PMC6601275; PMID: 31182572.