Tissue engineering and regenerative medicine is a multi-disciplinary and inter-disciplinary approach to develop engineered substitutes in the form of grafts or scaffolds to maintain, restore, and improve the functioning of tissues. The gold standard is to use auto-grafts, allografts, xenografts, but because of their supply shortage and other disadvantages like extended morbidity, two surgical sites, disease, and infection transfer make the research and development of alternatives an urgent need. Our research work in this field is mainly focused on the development of engineered bone grafts to treat maxillofacial, periodontal, and orthopedic bone defects, and translate these to human trials. Our lab is equipped with facilities like tissue engineering lab, good manufacturing practices lab, 3D printers (conventional and indigenously modified), freeze dryer, electrospinning set-up (conventional and indigenously modified), slow speed saw and other experimental facilities required for fabrication and testing. We have acquired several patents from our work and have published articles in peer-reviewed journals.
1) Biomimetic patient specific 3D printed bone grafts
A well-known advantage of 3D printing technology to build complex shapes is being used in our research work to develop patient specific bone grafts with customized 3D mesh. The scaffolds are made from composites of biocompatible polymers and ceramics. Not limited to synthetic polymers, we 3D print hydrogels made of natural polymers and ceramics by using an indigenously developed cryogenic 3D printer. Post treatments methods like freeze-drying and surface treatment induce nano surface roughness, surface porosity, and bulk porosity. The scaffolds have been proven biocompatible in vitro and produce chemicals relevant for early bone regeneration. The porous 3D scaffolds have shown better cellular attachment, proliferation, protein generation, and biomineralization in vitro. The simultaneous control of hierarchical structure from the overall shape, macro-porosity, internal 3D architecture, bulk microporosity, to nano surface roughness and spongy nature of the construct developed here with hard and soft materials makes their applications suitable for a potential bone graft for non-load bearing as well as load bearing bone defects.
2) 3D scaffold matrix
The developed novel 3D scaffolds from the unique combination of natural polymers and ceramics for bone regeneration. These scaffolds are highly porous and viscoelastic which can insert into any irregular defect and inhibits unexpected breakage thus facilitate oxygenation and angiogenesis. The 3D scaffold has active apatite nucleation sites and has mechanosensory surface for tissue interaction. The 3-D scaffold matrix’s in vivo study showed expedited healing of the defect by reconciling of cortico-trabecular bone formation with enhanced osteoblasts activity and mineralization. The 3-D scaffold matrix has been successfully implanted in human and is being evaluated for safety and efficacy. The composite along with differentiating features projects it as affordable effective treatment for bone regenerative applications.
3) Nanofibrous coated metallic implants
Commercial metallic implants such as titanium implant surface when coated with biodegradable, highly porous, osteogenic nanofibrous coating has shown enhanced intrinsic osteoinductive and osteoconductive properties. This coating mimics extracellular matrix resulting in differentiation of stem cells present in the peri-implant niche to osteoblast and hence results in enhanced osseointegration of the implant. In pre-clinical animal trials, the coated implant showed enhanced new bone formation when placed in the tibia of rabbit study models. The findings confirm that osteogenic nanofibrous coating significantly increases the magnitude of osteogenesis in the peri-implant zone and provides evidence of stronger and favourable bone bio-response resulting in noticeable promotion of osseointegration with respect to osteogenic nanofibrous coated titanium implants, when compared to metallic implants available commercially. Thus, the novel approach toward implant bone integration holds significant promise for its easy and economical coating thereby marking the beginning of new era of electrospun osteogenic nanofibrous coated bone implants.
4) 2D nano-fiber mat for tissue engineering
The advancement in nanotechnology has enabled the use of nanofibrous scaffold for bone tissue constructs. We develop two dimensional fiber mat porous structure that mimics extracellular (ECM) matrix of bone which provide support to cells and guide cellular behaviour. Synthetic polymers are used to provide strength and elasticity, and natural polymers have been blended to increase the biomimeticity of synthetic polymers. The composites have the advantages of both, improved biocompatibility, tunable mechanical properties and degradability. We are working to fabricate a bio-active high-performance polymers whose strength is superior in comparison with other electrospun polymer and combining the electrospun sheet with other scaffold forming techniques to achieve a scaffold that is load bearing and bio-resorbable. Electrospinning is also used for other tissues that requires two dimensional nanofibrous polymer composite sheet for faster restoration of their functions. Nano fillers doped electrospun fibers tested in vitro and in vivo exhibited faster and improved skin tissue wound healing in rodent animal model. Nanofibrous matrix also demonstrated haemostatic efficacy in a rat liver injury model. We are developing chemically modified electrospun membranes which have improved bioactivity and biodegradability by adding suitable polymer and nanofillers for faster restoring of tissue function.
5) Resorbable screw
The use of bioresorbable materials offers distinctive advantages in the field of orthopaedics. Musculoskeletal fixation devices like screws, plates, rods, nails, suture or anchors are extensively used in orthopaedic practice for bone-soft tissue indications like fractures, soft tissue fixations, arthrodesis and osteotomies. A novel composite biomaterial with incorporation of two fillers in PCL has been developed and has exhibited increased in vitro biocompatibility, ex vivo hemocompatibility, enhanced in vivo biocompatibility in rats, and increased pull-out strength in synthetic bone model. Thus, the composite bone screw prototype developed here from advanced biomaterial composite is a promising substitute for soft tissue fixations like ACL reconstruction.
Relevant journal publications for 3D printing of bone grafts
- Deepak Gupta, Atul Kumar Singh, Ashwin Dravid, and Jayesh Bellare. "Multiscale Porosity in Compressible Cryogenically 3D Printed Gels for Bone Tissue Engineering." ACS Applied Materials & Interfaces 11 (22) (2019): 20437-20452 [Link]
- Deepak Gupta, Atul Kumar Singh, Neelakshi Kar, Ashwin Dravid, and Jayesh Bellare. "Modelling and optimization of NaOH-etched 3-D printed PCL for enhanced cellular attachment and growth with minimal loss of mechanical strength." Materials Science and Engineering: C 98 (2019): 602-611 [Link]
Relevant journal publications for 3D Scaffold Matrix
- Nitin Sagar, Kunal Khanna, Varda S. Sardesai, Atul K. Singh, Mayur Temgire, Mridula Phukan Kalita, Sachin S. Kadam, Vivek P. Soni, Deepa Bhartiya, and Jayesh R. Bellare. "Bioconductive 3D nano-composite constructs with tunable elasticity to initiate stem cell growth and induce bone mineralization." Materials Science and Engineering: C 69 (2016): 700-714 [Link]
- Hemlata Chhabra, Jyoti Kumbhar, Jyutika Rajwade, Sachin Jadhav, Kishore Paknikar, Sameer Jadhav, and Jayesh R. Bellare. "Three-dimensional scaffold of gelatin–poly (methyl vinyl ether-alt-maleic anhydride) for regenerative medicine: Proliferation and differentiation of mesenchymal stem cells." Journal of Bioactive and Compatible Polymers 31 (3) (2016): 273-290 [Link]
- Hemlata Chhabra, Priyanka Gupta, Paul J. Verma, Sameer Jadhav, and Jayesh R. Bellare. "Gelatin–PMVE/MA composite scaffold promotes expansion of embryonic stem cells." Materials Science and Engineering: C 37 (2014): 184-194 [Link]
- Nitin Sagar, Alok K. Pandey, Deepak Gurbani, Kainat Khan, Dhirendra Singh, Bhushan P. Chaudhari, Vivek P. Soni, Naibedya Chattopadhyay, Alok Dhawan, and Jayesh R. Bellare. "In-vivo efficacy of compliant 3D nano-composite in critical-size bone defect repair: a six month preclinical study in rabbit." PloS One 8 (10) (2013) [Link]
- Nitin Sagar, Vivek P. Soni, and Jayesh R. Bellare. "Influence of carboxymethyl chitin on stability and biocompatibility of 3D nanohydroxyapatite/gelatin/carboxymethyl chitin composite for bone tissue engineering." Journal of Biomedical Materials Research Part B: Applied Biomaterials 100 (3) (2012): 624-636 [Link]
Relevant journal publications for nanofibrous coated metallic implants
- Siddhartha Das, Kanchan Dholam, Sandeep Gurav, Kiran Bendale, Arvind Ingle, Bhabani Mohanty, Pradip Chaudhari, and Jayesh R. Bellare. "Accentuated osseointegration in osteogenic nanofibrous coated titanium implants." Scientific Reports 9 (1) (2019): 1-14 [Link]
- Siddhartha Das, Sandeep Gurav, Vivek Soni, Arvind Ingle, Bhabani S. Mohanty, Pradip Chaudhari, Kiran Bendale, Kanchan Dholam, and Jayesh R. Bellare. "Osteogenic nanofibrous coated titanium implant results in enhanced osseointegration: in vivo preliminary study in a rabbit model." Tissue Engineering and Regenerative Medicine 15 (2) (2018): 231-247 [Link]
Relevant journal publications for 2D nano-fiber mat for tissue engineering
- Priya Vashisth, and Jayesh R. Bellare. "Development of hybrid scaffold with biomimetic 3D architecture for bone regeneration." Nanomedicine: Nanotechnology, Biology and Medicine 14 (4) (2018): 1325-1336 [Link]
- Siddhartha Das, and Jayesh R. Bellare. "Dental pulp stem cells in customized 3D nanofibrous scaffolds for regeneration of peripheral nervous system." Stem Cell Nanotechnology (2018) 157-166 [Link]
- Amit K. Jaiswal, Hemlata Chhabra, Sandipan Narwane, Nirmala Rege, and Jayesh R. Bellare. "Hemostatic efficacy of nanofibrous matrix in rat liver injury model." Surgical Innovation 24 (1) (2017): 23-28 [Link]
- Kunal Khanna, Amit Jaiswal, Rohit V. Dhumal, Nilakash Selkar, Pradip Chaudhari, Vivek P. Soni, Geeta R. Vanage, and Jayesh Bellare. "Comparative bone regeneration study of hardystonite and hydroxyapatite as filler in critical-sized defect of rat calvaria." RSC advances 7, no. 60 (2017): 37522-37533 [Link]
- Hemlata Chhabra, Rucha Deshpande, Meghana Kanitkar, Amit Jaiswal, Vaijayanti P. Kale, and Jayesh R. Bellare. "A nano zinc oxide doped electrospun scaffold improves wound healing in a rodent model." RSC Advances 6 (2 (2016): 1428-1439 [Link]
- Amit K. Jaiswal, Rohit V. Dhumal, Sandipto Ghosh, Pradip Chaudhari, Harishankar Nemani, Vivek P. Soni, Geeta R. Vanage, and Jayesh R. Bellare. "Bone healing evaluation of nanofibrous composite scaffolds in rat calvarial defects: a comparative study." Journal of Biomedical Nanotechnology 9 (12) (2013): 2073-2085 [Link]
- Amit K. Jaiswal, Rohit V. Dhumal, Jayesh R. Bellare, and Geeta R. Vanage. "In vivo biocompatibility evaluation of electrospun composite scaffolds by subcutaneous implantation in rat." Drug Delivery and Translational Research 3 (6) (2013): 504-517 [Link]
- Amit K. Jaiswal, Hemlata Chhabra, Sachin S. Kadam, Kishore Londhe, Vivek P. Soni, and Jayesh R. Bellare. "Hardystonite improves biocompatibility and strength of electrospun polycaprolactone nanofibers over hydroxyapatite: A comparative study." Materials Science and Engineering: C 33 (5) (2013): 2926-2936 [Link]
- A. K. Jaiswal, H. Chhabra, V. P. Soni, and J. R. Bellare. "Enhanced mechanical strength and biocompatibility of electrospun polycaprolactone-gelatin scaffold with surface deposited nano-hydroxyapatite." Materials Science and Engineering: C 33 (4) (2013): 2376-2385 [Link]
- Amit K. Jaiswal, Sachin S. Kadam, Vivek P. Soni, and Jayesh R. Bellare. "Improved functionalization of electrospun PLLA/gelatin scaffold by alternate soaking method for bone tissue engineering." Applied Surface Science 268 (2013): 477-488 [Link]
- Amit K. Jaiswal, Vikash Chandra, Ramesh R. Bhonde, Vivek Prithviraj Soni, and Jayesh Ramesh Bellare. "Mineralization of nanohydroxyapatite on electrospun poly (L-lactic acid)/gelatin by an alternate soaking process: A biomimetic scaffold for bone regeneration." Journal of Bioactive and Compatible Polymers 27 (4) (2012): 356-374 [Link]
Relevant journal publications for resorbable screw
- Ajay Suryavanshi, Kunal Khanna, K. R. Sindhu, Jayesh Bellare, and Rohit Srivastava. "Development of bone screw using novel biodegradable composite orthopedic biomaterial: from material design to in vitro biomechanical and in vivo biocompatibility evaluation." Biomedical Materials 14 (4) (2019): 045020 [Link]